Structural and functional differences between KRIT1A and KRIT1B isoforms: A framework for understanding CCM pathogenesis (525 views)
Exp Cell Res (ISSN: 0014-4827), 2009 Jan 15; 315(2): 285-303.
Export to BibTeX Export to EndNote
Paper type: Journal Article,
Impact factor: 3.589, 5-year impact factor: 3.713
Url: http://www.scopus.com/inward/record.url?eid=2-s2.0-57749178396&partnerID=40&md5=d60bd5ddefa5969cb63596d69c0a090d
Keywords: Ccm, Ferm Domain, Head-To-Tail Protein Interaction, Homology Modeling, Icap1, Krit1, Ligand Docking, Nucleocytoplasmic Shuttling, Rap1a, Yeast Two-Hybrid Interaction, Cell Protein, Protein Krit1a, Rap1 Protein, Rap1a Protein, Unclassified Drug, Animal Cell, Article, Brain Malformation, Cellular Distribution, Cerebral Cavernous Malformation, Controlled Study, Exon, Molecular Model, Nonhuman, Nucleotide Sequence, Pathogenesis, Priority Journal, Protein Binding, Protein Domain, Protein Localization, Protein Protein Interaction, Protein Structure, Protein Transport, Sequence Homology, Structure Activity Relation, Cell Line, Central Nervous System Vascular Malformations, Cercopithecus Aethiops, Computer Simulation, Cos Cells, Hela Cells, Hemangioma, Intracellular Signaling Peptides And Proteins, Microfilament Proteins, Microtubule-Associated Proteins, Peptide Fragments, Point Mutation, Protein Interaction Domains And Motifs, Protein Isoforms, Secondary, Proto-Oncogene Proteins, Rap1 Gtp-Binding Proteins, Recombinant Fusion Proteins, Two-Hybrid System Techniques,
Affiliations:
*** IBB - CNR ***
Molecular Biotechnology Centre, Department of Genetics, Biology and Biochemistry, Via Nizza 52, 10126 Torino, Italy
Department of Molecular Biology, University of Siena, Italy
Department of Chemistry IFM, University of Torino, Italy
Institute of Biostructure and Bioimaging, National Research Council of Napoli, Italy
References:
Serebriiskii, I., Estojak, J., Sonoda, G., Testa, J.R., Golemis, E.A., Association of Krev-1/rap1a with Krit1, a novel ankyrin repeat-containing protein encoded by a gene mapping to 7q21-22 (1997) Oncogene, 15, pp. 1043-104
Eerola, I., McIntyre, B., Vikkula, M., Identification of eight novel 5′-exons in cerebral capillary malformation gene-1 (CCM1) encoding KRIT1 (2001) Biochim. Biophys. Acta, 1517, pp. 464-467
Sahoo, T., Goenaga-Diaz, E., Serebriiskii, I.G., Thomas, J.W., Kotova, E., Cuellar, J.G., Peloquin, J.M., Marchuk, D.A., Computational and experimental analyses reveal previously undetected coding exons of the KRIT1 (CCM1) gene (2001) Genomics, 71, pp. 123-126
Zhang, J., Clatterbuck, R.E., Rigamonti, D., Dietz, H.C., Cloning of the murine Krit1 cDNA reveals novel mammalian 5′ coding exons (2000) Genomics, 70, pp. 392-395
Laberge-le Couteulx, S., Jung, H.H., Labauge, P., Houtteville, J.P., Lescoat, C., Cecillon, M., Marechal, E., Tournier-Lasserve, E., Truncating mutations in CCM1, encoding KRIT1, cause hereditary cavernous angiomas (1999) Nat. Genet., 23, pp. 189-193
Sahoo, T., Johnson, E.W., Thomas, J.W., Kuehl, P.M., Jones, T.L., Dokken, C.G., Touchman, J.W., Marchuk, D.A., Mutations in the gene encoding KRIT1, a Krev-1/rap1a binding protein, cause cerebral cavernous malformations (CCM1) (1999) Hum. Mol. Genet., 8, pp. 2325-2333
Felbor, U., Sure, U., Grimm, T., Bertalanffy, H., Genetics of cerebral cavernous angioma (2006) Zentralbl. Neurochir., 67, pp. 110-116
Labauge, P., Denier, C., Bergametti, F., Tournier-Lasserve, E., Genetics of cavernous angiomas (2007) Lancet Neurol., 6, pp. 237-244
Whitehead, K.J., Plummer, N.W., Adams, J.A., Marchuk, D.A., Li, D.Y., Ccm1 is required for arterial morphogenesis: implications for the etiology of human cavernous malformations (2004) Development, 131, pp. 1437-1448
Zawistowski, J.S., Serebriiskii, I.G., Lee, M.F., Golemis, E.A., Marchuk, D.A., KRIT1 association with the integrin-binding protein ICAP-1: a new direction in the elucidation of cerebral cavernous malformations (CCM1) pathogenesis (2002) Hum. Mol. Genet., 11, pp. 389-396
Zhang, J., Rigamonti, D., Dietz, H.C., Clatterbuck, R.E., Interaction between krit1 and malcavernin: implications for the pathogenesis of cerebral cavernous malformations (2007) Neurosurgery, 60, pp. 353-359. , discussion 359
Sedgwick, S.G., Smerdon, S.J., The ankyrin repeat: a diversity of interactions on a common structural framework (1999) Trends Biochem. Sci., 24, pp. 311-316
Balzac, F., Avolio, M., Degani, S., Kaverina, I., Torti, M., Silengo, L., Small, J.V., Retta, S.F., E-cadherin endocytosis regulates the activity of Rap1: a traffic light GTPase at the crossroads between cadherin and integrin function (2005) J. Cell Sci., 118, pp. 4765-4783
Retta, S.F., Balzac, F., Avolio, M., Rap1: a turnabout for the crosstalk between cadherins and integrins (2006) Eur. J. Cell Biol., 85, pp. 283-293
Glading, A., Han, J., Stockton, R.A., Ginsberg, M.H., KRIT-1/CCM1 is a Rap1 effector that regulates endothelial cell cell junctions (2007) J. Cell Biol., 179, pp. 247-254
Beraud-Dufour, S., Gautier, R., Albiges-Rizo, C., Chardin, P., Faurobert, E., Krit 1 interactions with microtubules and membranes are regulated by Rap1 and integrin cytoplasmic domain associated protein-1 (2007) FEBS J., 274, pp. 5518-5532
Pearson, M.A., Reczek, D., Bretscher, A., Karplus, P.A., Structure of the ERM protein moesin reveals the FERM domain fold masked by an extended actin binding tail domain (2000) Cell, 101, pp. 259-270
Ceccarelli, D.F., Song, H.K., Poy, F., Schaller, M.D., Eck, M.J., Crystal structure of the FERM domain of focal adhesion kinase (2006) J. Biol. Chem., 281, pp. 252-259
Garcia-Alvarez, B., de Pereda, J.M., Calderwood, D.A., Ulmer, T.S., Critchley, D., Campbell, I.D., Ginsberg, M.H., Liddington, R.C., Structural determinants of integrin recognition by talin (2003) Mol. Cell, 11, pp. 49-58
Hamada, K., Shimizu, T., Matsui, T., Tsukita, S., Hakoshima, T., Structural basis of the membrane-targeting and unmasking mechanisms of the radixin FERM domain (2000) EMBO J., 19, pp. 4449-4462
Han, B.G., Nunomura, W., Wu, H., Mohandas, N., Jap, B.K., Crystallization and preliminary X-ray crystallographic analysis of the 30 kDa membrane-binding domain of protein 4.1 from human erythrocytes (2000) Acta Crystallogr. D. Biol. Crystallogr., 56, pp. 187-188
Shimizu, T., Seto, A., Maita, N., Hamada, K., Tsukita, S., Hakoshima, T., Structural basis for neurofibromatosis type 2. Crystal structure of the merlin FERM domain (2002) J. Biol. Chem., 277, pp. 10332-10336
Smith, W.J., Nassar, N., Bretscher, A., Cerione, R.A., Karplus, P.A., Structure of the active N-terminal domain of Ezrin. Conformational and mobility changes identify keystone interactions (2003) J. Biol. Chem., 278, pp. 4949-4956
Retta, S.F., Avolio, M., Francalanci, F., Procida, S., Balzac, F., Degani, S., Tarone, G., Silengo, L., Identification of Krit1B: a novel alternative splicing isoform of cerebral cavernous malformation gene-1 (2004) Gene, 325, pp. 63-78
Cave-Riant, F., Denier, C., Labauge, P., Cecillon, M., Maciazek, J., Joutel, A., Laberge-Le Couteulx, S., Tournier-Lasserve, E., Spectrum and expression analysis of KRIT1 mutations in 121 consecutive and unrelated patients with cerebral cavernous malformations (2002) Eur. J. Hum. Genet., 10, pp. 733-740
Stahl, S., Gaetzner, S., Voss, K., Brackertz, B., Schleider, E., Surucu, O., Kunze, E., Felbor, U., Novel CCM1, CCM2, and CCM3 mutations in patients with cerebral cavernous malformations: in-frame deletion in CCM2 prevents formation of a CCM1/CCM2/CCM3 protein complex (2008) Human Mutat., 29, pp. 709-717
Thompson, J.D., Higgins, D.G., Gibson, T.J., CLUSTAL W: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties and weight matrix choice (1994) Nucleic Acids Res., 22, pp. 4673-4680
Kang, B.S., Cooper, D.R., Devedjiev, Y., Derewenda, U., Derewenda, Z.S., The structure of the FERM domain of merlin, the neurofibromatosis type 2 gene product (2002) Acta Crystallogr. D. Biol. Crystallogr., 58, pp. 381-391
Sippl, M.J., Recognition of errors in three-dimensional structures of proteins (1993) Proteins, 17, pp. 355-362
Hooft, R.W., Vriend, G., Sander, C., Abola, E.E., Errors in protein structures (1996) Nature, 381, p. 272
Cornell, W.D., Cieplak, P., Bayly, C.I., Gould, I.R., Merz, K.M., Ferguson, D.M., Spellmeyer, D.C., Kollman, P.A., A second-generation force field for the simulation of proteins, nucleic acids, and organic molecules (1995) J. Am. Chem. Soc., 117, pp. 5179-5197
Halgren, T.A., Merck molecular force field. I. Basis, form, scope, parameterization, and performance of MMFF94 (1996) J. Comput. Chem., 17, pp. 490-519
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Toby, G.G., Golemis, E.A., Using the yeast interaction trap and other two-hybrid-based approaches to study protein-protein interactions (2001) Methods, 24, pp. 201-217
Kelley, L.A., MacCallum, R.M., Sternberg, M.J., Enhanced genome annotation using structural profiles in the program 3D-PSSM (2000) J. Mol. Biol., 299, pp. 499-520
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Yan, K.S., Kuti, M., Zhou, M.M., PTB or not PTB-that is the question (2002) FEBS Lett., 513, pp. 67-70
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Calderwood, D.A., Fujioka, Y., de Pereda, J.M., Garcia-Alvarez, B., Nakamoto, T., Margolis, B., McGlade, C.J., Ginsberg, M.H., Integrin beta cytoplasmic domain interactions with phosphotyrosine-binding domains: a structural prototype for diversity in integrin signaling (2003) Proc. Natl. Acad. Sci. U. S. A., 100, pp. 2272-2277
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Pufall, M.A., Graves, B.J., Autoinhibitory domains: modular effectors of cellular regulation (2002) Annu. Rev. Cell Dev. Biol., 18, pp. 421-462
Li, Q., Nance, M.R., Kulikauskas, R., Nyberg, K., Fehon, R., Karplus, P.A., Bretscher, A., Tesmer, J.J., Self-masking in an intact ERM-merlin protein: an active role for the central alpha-helical domain (2007) J. Mol. Biol., 365, pp. 1446-1459
Bretscher, A., Edwards, K., Fehon, R.G., ERM proteins and merlin: integrators at the cell cortex (2002) Nat. Rev., Mol. Cell Biol., 3, pp. 586-599
Kressel, M., Schmucker, B., Nucleocytoplasmic transfer of the NF2 tumor suppressor protein merlin is regulated by exon 2 and a CRM1-dependent nuclear export signal in exon 15 (2002) Hum. Mol. Genet., 11, pp. 2269-2278
Luque, C.M., Correas, I., A constitutive region is responsible for nuclear targeting of 4.1R: modulation by alternative sequences results in differential intracellular localization (2000) J. Cell Sci., 113 (PART 13), pp. 2485-2495
Kaffman, A., O'Shea, E.K., Regulation of nuclear localization: a key to a door (1999) Annu. Rev. Cell Dev. Biol., 15, pp. 291-339
Whitehead, K. J., Plummer, N. W., Adams, J. A., Marchuk, D. A., Li, D. Y., Ccm1 is required for arterial morphogenesis: implications for the etiology of human cavernous malformations (2004) Development, 131, pp. 1437-1448
Zawistowski, J. S., Serebriiskii, I. G., Lee, M. F., Golemis, E. A., Marchuk, D. A., KRIT1 association with the integrin-binding protein ICAP-1: a new direction in the elucidation of cerebral cavernous malformations (CCM1) pathogenesis (2002) Hum. Mol. Genet., 11, pp. 389-396
Sedgwick, S. G., Smerdon, S. J., The ankyrin repeat: a diversity of interactions on a common structural framework (1999) Trends Biochem. Sci., 24, pp. 311-316
Retta, S. F., Balzac, F., Avolio, M., Rap1: a turnabout for the crosstalk between cadherins and integrins (2006) Eur. J. Cell Biol., 85, pp. 283-293
Pearson, M. A., Reczek, D., Bretscher, A., Karplus, P. A., Structure of the ERM protein moesin reveals the FERM domain fold masked by an extended actin binding tail domain (2000) Cell, 101, pp. 259-270
Ceccarelli, D. F., Song, H. K., Poy, F., Schaller, M. D., Eck, M. J., Crystal structure of the FERM domain of focal adhesion kinase (2006) J. Biol. Chem., 281, pp. 252-259
Han, B. G., Nunomura, W., Wu, H., Mohandas, N., Jap, B. K., Crystallization and preliminary X-ray crystallographic analysis of the 30 kDa membrane-binding domain of protein 4. 1 from human erythrocytes (2000) Acta Crystallogr. D. Biol. Crystallogr., 56, pp. 187-188
Smith, W. J., Nassar, N., Bretscher, A., Cerione, R. A., Karplus, P. A., Structure of the active N-terminal domain of Ezrin. Conformational and mobility changes identify keystone interactions (2003) J. Biol. Chem., 278, pp. 4949-4956
Retta, S. F., Avolio, M., Francalanci, F., Procida, S., Balzac, F., Degani, S., Tarone, G., Silengo, L., Identification of Krit1B: a novel alternative splicing isoform of cerebral cavernous malformation gene-1 (2004) Gene, 325, pp. 63-78
Thompson, J. D., Higgins, D. G., Gibson, T. J., CLUSTAL W: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties and weight matrix choice (1994) Nucleic Acids Res., 22, pp. 4673-4680
Kang, B. S., Cooper, D. R., Devedjiev, Y., Derewenda, U., Derewenda, Z. S., The structure of the FERM domain of merlin, the neurofibromatosis type 2 gene product (2002) Acta Crystallogr. D. Biol. Crystallogr., 58, pp. 381-391
Sippl, M. J., Recognition of errors in three-dimensional structures of proteins (1993) Proteins, 17, pp. 355-362
Hooft, R. W., Vriend, G., Sander, C., Abola, E. E., Errors in protein structures (1996) Nature, 381, p. 272
Cornell, W. D., Cieplak, P., Bayly, C. I., Gould, I. R., Merz, K. M., Ferguson, D. M., Spellmeyer, D. C., Kollman, P. A., A second-generation force field for the simulation of proteins, nucleic acids, and organic molecules (1995) J. Am. Chem. Soc., 117, pp. 5179-5197
Halgren, T. A., Merck molecular force field. I. Basis, form, scope, parameterization, and performance of MMFF94 (1996) J. Comput. Chem., 17, pp. 490-519
Toby, G. G., Golemis, E. A., Using the yeast interaction trap and other two-hybrid-based approaches to study protein-protein interactions (2001) Methods, 24, pp. 201-217
Kelley, L. A., MacCallum, R. M., Sternberg, M. J., Enhanced genome annotation using structural profiles in the program 3D-PSSM (2000) J. Mol. Biol., 299, pp. 499-520
Forman-Kay, J. D., Pawson, T., Diversity in protein recognition by PTB domains (1999) Curr. Opin. Struct. Biol., 9, pp. 690-695
Uhlik, M. T., Temple, B., Bencharit, S., Kimple, A. J., Siderovski, D. P., Johnson, G. L., Structural and evolutionary division of phosphotyrosine binding (PTB) domains (2005) J. Mol. Biol., 345, pp. 1-20
Yan, K. S., Kuti, M., Zhou, M. M., PTB or not PTB-that is the question (2002) FEBS Lett., 513, pp. 67-70
Campbell, S. J., Gold, N. D., Jackson, R. M., Westhead, D. R., Ligand binding: functional site location, similarity and docking (2003) Curr. Opin. Struct. Biol., 13, pp. 389-395
Calderwood, D. A., Fujioka, Y., de Pereda, J. M., Garcia-Alvarez, B., Nakamoto, T., Margolis, B., McGlade, C. J., Ginsberg, M. H., Integrin beta cytoplasmic domain interactions with phosphotyrosine-binding domains: a structural prototype for diversity in integrin signaling (2003) Proc. Natl. Acad. Sci. U. S. A., 100, pp. 2272-2277
Pufall, M. A., Graves, B. J., Autoinhibitory domains: modular effectors of cellular regulation (2002) Annu. Rev. Cell Dev. Biol., 18, pp. 421-462
Li, Q., Nance, M. R., Kulikauskas, R., Nyberg, K., Fehon, R., Karplus, P. A., Bretscher, A., Tesmer, J. J., Self-masking in an intact ERM-merlin protein: an active role for the central alpha-helical domain (2007) J. Mol. Biol., 365, pp. 1446-1459
Luque, C. M., Correas, I., A constitutive region is responsible for nuclear targeting of 4. 1R: modulation by alternative sequences results in differential intracellular localization (2000) J. Cell Sci., 113 (PART 13), pp. 2485-2495
Exp Cell Res (ISSN: 0014-4827), 2009 Jan 15; 315(2): 285-303.
Export to BibTeX Export to EndNote
Paper type: Journal Article,
Impact factor: 3.589, 5-year impact factor: 3.713
Url: http://www.scopus.com/inward/record.url?eid=2-s2.0-57749178396&partnerID=40&md5=d60bd5ddefa5969cb63596d69c0a090d
Keywords: Ccm, Ferm Domain, Head-To-Tail Protein Interaction, Homology Modeling, Icap1, Krit1, Ligand Docking, Nucleocytoplasmic Shuttling, Rap1a, Yeast Two-Hybrid Interaction, Cell Protein, Protein Krit1a, Rap1 Protein, Rap1a Protein, Unclassified Drug, Animal Cell, Article, Brain Malformation, Cellular Distribution, Cerebral Cavernous Malformation, Controlled Study, Exon, Molecular Model, Nonhuman, Nucleotide Sequence, Pathogenesis, Priority Journal, Protein Binding, Protein Domain, Protein Localization, Protein Protein Interaction, Protein Structure, Protein Transport, Sequence Homology, Structure Activity Relation, Cell Line, Central Nervous System Vascular Malformations, Cercopithecus Aethiops, Computer Simulation, Cos Cells, Hela Cells, Hemangioma, Intracellular Signaling Peptides And Proteins, Microfilament Proteins, Microtubule-Associated Proteins, Peptide Fragments, Point Mutation, Protein Interaction Domains And Motifs, Protein Isoforms, Secondary, Proto-Oncogene Proteins, Rap1 Gtp-Binding Proteins, Recombinant Fusion Proteins, Two-Hybrid System Techniques,
Affiliations:
*** IBB - CNR ***
Molecular Biotechnology Centre, Department of Genetics, Biology and Biochemistry, Via Nizza 52, 10126 Torino, Italy
Department of Molecular Biology, University of Siena, Italy
Department of Chemistry IFM, University of Torino, Italy
Institute of Biostructure and Bioimaging, National Research Council of Napoli, Italy
References:
Serebriiskii, I., Estojak, J., Sonoda, G., Testa, J.R., Golemis, E.A., Association of Krev-1/rap1a with Krit1, a novel ankyrin repeat-containing protein encoded by a gene mapping to 7q21-22 (1997) Oncogene, 15, pp. 1043-104
Eerola, I., McIntyre, B., Vikkula, M., Identification of eight novel 5′-exons in cerebral capillary malformation gene-1 (CCM1) encoding KRIT1 (2001) Biochim. Biophys. Acta, 1517, pp. 464-467
Sahoo, T., Goenaga-Diaz, E., Serebriiskii, I.G., Thomas, J.W., Kotova, E., Cuellar, J.G., Peloquin, J.M., Marchuk, D.A., Computational and experimental analyses reveal previously undetected coding exons of the KRIT1 (CCM1) gene (2001) Genomics, 71, pp. 123-126
Zhang, J., Clatterbuck, R.E., Rigamonti, D., Dietz, H.C., Cloning of the murine Krit1 cDNA reveals novel mammalian 5′ coding exons (2000) Genomics, 70, pp. 392-395
Laberge-le Couteulx, S., Jung, H.H., Labauge, P., Houtteville, J.P., Lescoat, C., Cecillon, M., Marechal, E., Tournier-Lasserve, E., Truncating mutations in CCM1, encoding KRIT1, cause hereditary cavernous angiomas (1999) Nat. Genet., 23, pp. 189-193
Sahoo, T., Johnson, E.W., Thomas, J.W., Kuehl, P.M., Jones, T.L., Dokken, C.G., Touchman, J.W., Marchuk, D.A., Mutations in the gene encoding KRIT1, a Krev-1/rap1a binding protein, cause cerebral cavernous malformations (CCM1) (1999) Hum. Mol. Genet., 8, pp. 2325-2333
Felbor, U., Sure, U., Grimm, T., Bertalanffy, H., Genetics of cerebral cavernous angioma (2006) Zentralbl. Neurochir., 67, pp. 110-116
Labauge, P., Denier, C., Bergametti, F., Tournier-Lasserve, E., Genetics of cavernous angiomas (2007) Lancet Neurol., 6, pp. 237-244
Whitehead, K.J., Plummer, N.W., Adams, J.A., Marchuk, D.A., Li, D.Y., Ccm1 is required for arterial morphogenesis: implications for the etiology of human cavernous malformations (2004) Development, 131, pp. 1437-1448
Zawistowski, J.S., Serebriiskii, I.G., Lee, M.F., Golemis, E.A., Marchuk, D.A., KRIT1 association with the integrin-binding protein ICAP-1: a new direction in the elucidation of cerebral cavernous malformations (CCM1) pathogenesis (2002) Hum. Mol. Genet., 11, pp. 389-396
Zhang, J., Rigamonti, D., Dietz, H.C., Clatterbuck, R.E., Interaction between krit1 and malcavernin: implications for the pathogenesis of cerebral cavernous malformations (2007) Neurosurgery, 60, pp. 353-359. , discussion 359
Sedgwick, S.G., Smerdon, S.J., The ankyrin repeat: a diversity of interactions on a common structural framework (1999) Trends Biochem. Sci., 24, pp. 311-316
Balzac, F., Avolio, M., Degani, S., Kaverina, I., Torti, M., Silengo, L., Small, J.V., Retta, S.F., E-cadherin endocytosis regulates the activity of Rap1: a traffic light GTPase at the crossroads between cadherin and integrin function (2005) J. Cell Sci., 118, pp. 4765-4783
Retta, S.F., Balzac, F., Avolio, M., Rap1: a turnabout for the crosstalk between cadherins and integrins (2006) Eur. J. Cell Biol., 85, pp. 283-293
Glading, A., Han, J., Stockton, R.A., Ginsberg, M.H., KRIT-1/CCM1 is a Rap1 effector that regulates endothelial cell cell junctions (2007) J. Cell Biol., 179, pp. 247-254
Beraud-Dufour, S., Gautier, R., Albiges-Rizo, C., Chardin, P., Faurobert, E., Krit 1 interactions with microtubules and membranes are regulated by Rap1 and integrin cytoplasmic domain associated protein-1 (2007) FEBS J., 274, pp. 5518-5532
Pearson, M.A., Reczek, D., Bretscher, A., Karplus, P.A., Structure of the ERM protein moesin reveals the FERM domain fold masked by an extended actin binding tail domain (2000) Cell, 101, pp. 259-270
Ceccarelli, D.F., Song, H.K., Poy, F., Schaller, M.D., Eck, M.J., Crystal structure of the FERM domain of focal adhesion kinase (2006) J. Biol. Chem., 281, pp. 252-259
Garcia-Alvarez, B., de Pereda, J.M., Calderwood, D.A., Ulmer, T.S., Critchley, D., Campbell, I.D., Ginsberg, M.H., Liddington, R.C., Structural determinants of integrin recognition by talin (2003) Mol. Cell, 11, pp. 49-58
Hamada, K., Shimizu, T., Matsui, T., Tsukita, S., Hakoshima, T., Structural basis of the membrane-targeting and unmasking mechanisms of the radixin FERM domain (2000) EMBO J., 19, pp. 4449-4462
Han, B.G., Nunomura, W., Wu, H., Mohandas, N., Jap, B.K., Crystallization and preliminary X-ray crystallographic analysis of the 30 kDa membrane-binding domain of protein 4.1 from human erythrocytes (2000) Acta Crystallogr. D. Biol. Crystallogr., 56, pp. 187-188
Shimizu, T., Seto, A., Maita, N., Hamada, K., Tsukita, S., Hakoshima, T., Structural basis for neurofibromatosis type 2. Crystal structure of the merlin FERM domain (2002) J. Biol. Chem., 277, pp. 10332-10336
Smith, W.J., Nassar, N., Bretscher, A., Cerione, R.A., Karplus, P.A., Structure of the active N-terminal domain of Ezrin. Conformational and mobility changes identify keystone interactions (2003) J. Biol. Chem., 278, pp. 4949-4956
Retta, S.F., Avolio, M., Francalanci, F., Procida, S., Balzac, F., Degani, S., Tarone, G., Silengo, L., Identification of Krit1B: a novel alternative splicing isoform of cerebral cavernous malformation gene-1 (2004) Gene, 325, pp. 63-78
Cave-Riant, F., Denier, C., Labauge, P., Cecillon, M., Maciazek, J., Joutel, A., Laberge-Le Couteulx, S., Tournier-Lasserve, E., Spectrum and expression analysis of KRIT1 mutations in 121 consecutive and unrelated patients with cerebral cavernous malformations (2002) Eur. J. Hum. Genet., 10, pp. 733-740
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Kang, B. S., Cooper, D. R., Devedjiev, Y., Derewenda, U., Derewenda, Z. S., The structure of the FERM domain of merlin, the neurofibromatosis type 2 gene product (2002) Acta Crystallogr. D. Biol. Crystallogr., 58, pp. 381-391
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Halgren, T. A., Merck molecular force field. I. Basis, form, scope, parameterization, and performance of MMFF94 (1996) J. Comput. Chem., 17, pp. 490-519
Toby, G. G., Golemis, E. A., Using the yeast interaction trap and other two-hybrid-based approaches to study protein-protein interactions (2001) Methods, 24, pp. 201-217
Kelley, L. A., MacCallum, R. M., Sternberg, M. J., Enhanced genome annotation using structural profiles in the program 3D-PSSM (2000) J. Mol. Biol., 299, pp. 499-520
Forman-Kay, J. D., Pawson, T., Diversity in protein recognition by PTB domains (1999) Curr. Opin. Struct. Biol., 9, pp. 690-695
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Structural and functional differences between KRIT1A and KRIT1B isoforms: A framework for understanding CCM pathogenesis
KRIT1 is a disease gene responsible for Cerebral Cavernous Malformations (CCM). It encodes for a protein containing distinct protein-protein interaction domains, including three NPXY/F motifs and a FERM domain. Previously, we isolated KRIT1B, an isoform characterized by the alternative splicing of the 15th coding exon and suspected to cause CCM when abnormally expressed. Combining homology modeling and docking methods of protein-structure and ligand binding prediction with the yeast two-hybrid assay of in vivo protein-protein interaction and cellular biology analyses we identified both structural and functional differences between KRIT1A and KRIT1B isoforms. We found that the 15th exon encodes for the distal β-sheet of the F3/PTB-like subdomain of KRIT1A FERM domain, demonstrating that KRIT1B is devoid of a functional PTB binding pocket. As major functional consequence, KRIT1B is unable to bind Rap1A, while the FERM domain of KRIT1A is even sufficient for this function. Furthermore, we found that a functional PTB subdomain enables the nucleocytoplasmic shuttling of KRIT1A, while its alteration confers a restricted cytoplasmic localization and a dominant negative role to KRIT1B. Importantly, we also demonstrated that KRIT1A, but not KRIT1B, may adopt a closed conformation through an intramolecular interaction involving the third NPXY/F motif at the N-terminus and the PTB subdomain of the FERM domain, and proposed a mechanism whereby an open/closed conformation switch regulates KRIT1A nuclear translocation and interaction with Rap1A in a mutually exclusive manner. As most mutations found in CCM patients affect the KRIT1 FERM domain, the new insights into the structure-function relationship of this domain may constitute a useful framework for understanding molecular mechanisms underlying CCM pathogenesis. © 2008 Elsevier Inc. All rights reserved.
KRIT1 is a disease gene responsible for Cerebral Cavernous Malformations (CCM). It encodes for a protein containing distinct protein-protein interaction domains, including three NPXY/F motifs and a FERM domain. Previously, we isolated KRIT1B, an isoform characterized by the alternative splicing of the 15th coding exon and suspected to cause CCM when abnormally expressed. Combining homology modeling and docking methods of protein-structure and ligand binding prediction with the yeast two-hybrid assay of in vivo protein-protein interaction and cellular biology analyses we identified both structural and functional differences between KRIT1A and KRIT1B isoforms. We found that the 15th exon encodes for the distal β-sheet of the F3/PTB-like subdomain of KRIT1A FERM domain, demonstrating that KRIT1B is devoid of a functional PTB binding pocket. As major functional consequence, KRIT1B is unable to bind Rap1A, while the FERM domain of KRIT1A is even sufficient for this function. Furthermore, we found that a functional PTB subdomain enables the nucleocytoplasmic shuttling of KRIT1A, while its alteration confers a restricted cytoplasmic localization and a dominant negative role to KRIT1B. Importantly, we also demonstrated that KRIT1A, but not KRIT1B, may adopt a closed conformation through an intramolecular interaction involving the third NPXY/F motif at the N-terminus and the PTB subdomain of the FERM domain, and proposed a mechanism whereby an open/closed conformation switch regulates KRIT1A nuclear translocation and interaction with Rap1A in a mutually exclusive manner. As most mutations found in CCM patients affect the KRIT1 FERM domain, the new insights into the structure-function relationship of this domain may constitute a useful framework for understanding molecular mechanisms underlying CCM pathogenesis. © 2008 Elsevier Inc. All rights reserved.
Structural and functional differences between KRIT1A and KRIT1B isoforms: A framework for understanding CCM pathogenesis
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Structural and functional differences between KRIT1A and KRIT1B isoforms: A framework for understanding CCM pathogenesis
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De Simone G, Di Fiore A, Capasso C, Supuran CT
* The zinc coordination pattern in the eta-carbonic anhydrase from Plasmodium falciparum is different from all other carbonic anhydrase genetic families (472 views)
Bioorg Med Chem Lett (ISSN: 0960-894x), 2015 Apr 1; 25(7): 1385-1389.
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Calvanese L, Marasco D, Doti N, Saporito A, D'Auria G, Paolillo L, Ruvo M, Falcigno L
* Structural Investigations on the Nodal-Cripto Binding: A Theoretical and Experimental Approach (596 views)
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Alfieri A, Pasanisi F, Salzano S, Esposito L, Martone D, Tafuri D, Daniele A, Contaldo F, Sacchetti L, Zagari A, Buono P
* Functional analysis of melanocortin-4-receptor mutants identified in severely obese subjects living in Southern Italy (397 views)
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Impact Factor: 2.266
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Palmieri G, Catara G, Saviano M, Langella E, Gogliettino M, Rossi M
* First archaeal PEPB-serine protease inhibitor from sulfolobus solfataricus with noncanonical amino acid sequence in the reactive-site loop (399 views)
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Impact Factor: 5.132
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Ragno R, Simeoni S, Castellano S, Vicidomini C, Mai A, Caroli A, Tramontano A, Bonaccini C, Trojer P, Bauer I, Brosch G, Sbardella G
* Small molecule inhibitors of histone arginine methyltransferases: Homology modeling, molecular docking, binding mode analysis, and biological evaluations (980 views)
J Med Chem (ISSN: 0022-2623, 1520-4804, 0022-2623print), 2007 Mar 22; 50(6): 1241-1253.
Impact Factor: 4.895
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* The zinc coordination pattern in the eta-carbonic anhydrase from Plasmodium falciparum is different from all other carbonic anhydrase genetic families (472 views)
Bioorg Med Chem Lett (ISSN: 0960-894x), 2015 Apr 1; 25(7): 1385-1389.
Impact Factor: 2.486
View Export to BibTeX Export to EndNote
Calvanese L, Marasco D, Doti N, Saporito A, D'Auria G, Paolillo L, Ruvo M, Falcigno L
* Structural Investigations on the Nodal-Cripto Binding: A Theoretical and Experimental Approach (596 views)
Biopolymers (ISSN: 0006-3525, 0006-6352, 0006-3525print), 2010 Nov; 93(11): 1011-1021.
Impact Factor: 2.572
View Export to BibTeX Export to EndNote
Alfieri A, Pasanisi F, Salzano S, Esposito L, Martone D, Tafuri D, Daniele A, Contaldo F, Sacchetti L, Zagari A, Buono P
* Functional analysis of melanocortin-4-receptor mutants identified in severely obese subjects living in Southern Italy (397 views)
Gene (ISSN: 0378-1119), 2010 Jun 1; 457(1-2): 35-41.
Impact Factor: 2.266
View Export to BibTeX Export to EndNote
Palmieri G, Catara G, Saviano M, Langella E, Gogliettino M, Rossi M
* First archaeal PEPB-serine protease inhibitor from sulfolobus solfataricus with noncanonical amino acid sequence in the reactive-site loop (399 views)
J Proteome Res (ISSN: 1535-3893), 2009 Jan; 8(1): 327-334.
Impact Factor: 5.132
View Export to BibTeX Export to EndNote
Ragno R, Simeoni S, Castellano S, Vicidomini C, Mai A, Caroli A, Tramontano A, Bonaccini C, Trojer P, Bauer I, Brosch G, Sbardella G
* Small molecule inhibitors of histone arginine methyltransferases: Homology modeling, molecular docking, binding mode analysis, and biological evaluations (980 views)
J Med Chem (ISSN: 0022-2623, 1520-4804, 0022-2623print), 2007 Mar 22; 50(6): 1241-1253.
Impact Factor: 4.895
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5 Records (5 excluding Abstracts).
Total impact factor: 17.351 (17.351 excluding Abstracts).
Total 5 year impact factor: 17.889 (17.889 excluding Abstracts).
Total impact factor: 17.351 (17.351 excluding Abstracts).
Total 5 year impact factor: 17.889 (17.889 excluding Abstracts).
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