Insights into structure, stability, and toxicity of monomeric and aggregated polyglutamine models from molecular dynamics simulations(416 views) Esposito L, Paladino A, Pedone C, Vitagliano L
Biophysical Journal (ISSN: 1542-0086, 0006-3495), 2008 May 15; 94(10): 4031-4040.
Keywords: Peptide, Polyglutamine, Article, Chemical Model, Chemical Structure, Chemistry, Computer Simulation, Conformation, Macromolecule, Macromolecular Substances, Molecular Conformation,
Affiliations: *** IBB - CNR ***
Istituto di Biostrutture e Bioimmagini, CNR, I-80134 Naples, Italy. luciana.esposito@unina.it
Laboratorio di Bioinformatica e Biologia Molecolare, Istituto di Scienze Alimentari, CNR, I-83100 Avellino, Italy
Dipartimento Delle Scienze Biologiche-Sezione di Biostrutture, Università degli Studi di Napoli Federico II, I-80134 Naples, Italy
References: Chiti, F., Dobson, C.M., Protein misfolding, functional amyloid, and human disease (2006) Annu. Rev. Biochem, 75, pp. 333-36
Buxbaum, J.N., Diseases of protein conformation: What do in vitro experiments tell us about in vivo diseases? (2003) Trends Biochem. Sci, 28, pp. 585-592
Ross, C.A., Poirier, M.A., Protein aggregation and neurodegenerative disease (2004) Nat. Med, 10 (SUPPL.), pp. S10-S17
Carrell, R.W., Cell toxicity and conformational disease (2005) Trends Cell Biol, 15, pp. 574-580
Kayed, R., Head, E., Thompson, J.L., McIntire, T.M., Milton, S.C., Cotman, C.W., Glabe, C.G., Common structure of soluble amyloid oligomers implies common mechanism of pathogenesis (2003) Science, 300, pp. 486-489
Gatchel, J.R., Zoghbi, H.Y., Diseases of unstable repeat expansion: Mechanisms and common principles (2005) Nat. Rev. Genet, 6, pp. 743-755
Brown, L.Y., Brown, S.A., Alanine tracts: The expanding story of human illness and trinucleotide repeats (2004) Trends Genet, 20, pp. 51-58
Perutz, M.F., Glutamine repeats and neurodegenerative diseases: Molecular aspects (1999) Trends Biochem. Sci, 24, pp. 58-63
Ross, C.A., Polyglutamine pathogenesis: Emergence of unifying mechanisms for Huntington's disease and related disorders (2002) Neuron, 35, pp. 819-822
Sikorski, P., Atkins, E., New model for crystalline polyglutamine assemblies and their connection with amyloid fibrils (2005) Biomac- romolecules, 6, pp. 425-432
Sharma, D., Shinchuk, L.M., Inouye, H., Wetzel, R., Kirschner, D.A., Polyglutamine homopolymers having 8-45 residues form slablike beta-crystallite assemblies (2005) Proteins, 61, pp. 398-411
Bader, R., Seeliger, M.A., Kelly, S.E., Ilag, L.L., Meersman, F., Limones, A., Luisi, B.F., Itzhaki, L.S., Folding and fibril formation of the cell cycle protein Cks1 (2006) J. Biol. Chem, 281, pp. 18816-18824
Tanaka, M., Machida, Y., Nishikawa, Y., Akagi, T., Hashikawa, T., Fujisawa, T., Nukina, N., Expansion of polyglutamine induces the formation of quasi-aggregate in the early stage of protein fibrillization (2003) J. Biol. Chem, 278, pp. 34717-34724
Bhattacharyya, A.M., Thakur, A.K., Wetzel, R., polyglutamine aggregation nucleation: Thermodynamics of a highly unfavorable protein folding reaction (2005) Proc. Natl. Acad. Sci. USA, 102, pp. 15400-15405
Wetzel, R., Kinetics and thermodynamics of amyloid fibril assembly (2006) Acc. Chem. Res, 39, pp. 671-679
Nagai, Y., Inui, T., Popiel, H.A., Fujikake, N., Hasegawa, K., Urade, Y., Goto, Y., Toda, T., A toxic monomeric conformer of the polyglutamine protein (2007) Nat. Struct. Mol. Biol, 14, pp. 332-340
Perutz, M.F., Pope, B.J., Owen, D., Wanker, E.E., Scherzinger, E., Aggregation of proteins with expanded glutamine and alanine repeats of the glutamine-rich and asparagine-rich domains of Sup35 and of the amyloid beta-peptide of amyloid plaques (2002) Proc. Natl. Acad. Sci. USA, 99, pp. 5596-5600
Merlino, A., Esposito, L., Vitagliano, L., Polyglutamine repeats and beta-helix structure: Molecular dynamics study (2006) Proteins, 63, pp. 918-927
Zanuy, D., Gunasekaran, K., Lesk, A.M., Nussinov, R., Computational study of the fibril organization of polyglutamine repeats reveals a common motif identified in beta-helices (2006) J. Mol. Biol, 358, pp. 330-345
Stork, M., Giese, A., Kretzschmar, H.A., Tavan, P., Molecular dynamics simulations indicate a possible role of parallel beta-helices in seeded aggregation of poly-Gln (2005) Biophys. J, 88, pp. 2442-2451
Armen, R.S., Bernard, B.M., Day, R., Alonso, D.O., Daggett, V., Characterization of a possible amyloidogenic precursor in glutamine-repeat neurodegenerative diseases (2005) Proc. Natl. Acad. Sci. USA, 102, pp. 13433-13438
Marchut, A.J., Hall, C.K., Effects of chain length on the aggregation of model polyglutamine peptides: Molecular dynamics simulations (2007) Proteins, 66, pp. 96-109
Sambashivan, S., Liu, Y., Sawaya, M.R., Gingery, M., Eisenberg, D., Amyloid-like fibrils of ribonuclease A with three-dimensional domain-swapped and native-like structure (2005) Nature, 437, pp. 266-269
Temussi, P.A., Masino, L., Pastore, A., From Alzheimer to Huntington: Why is a structural understanding so difficult? (2003) EMBO J, 22, pp. 355-361
Nelson, R., Sawaya, M.R., Balbirnie, M., Madsen, A.O., Riekel, C., Grothe, R., Eisenberg, D., Structure of the cross-beta spine of amyloid-like fibrils (2005) Nature, 435, pp. 773-778
Eisenberg, D., Nelson, R., Sawaya, M.R., Balbirnie, M., Sambashivan, S., Ivanova, M.I., Madsen, A.O., Riekel, C., The structuralbiology of protein aggregation diseases: Fundamental questions and some answers (2006) Acc. Chem. Res, 39, pp. 568-575
Sawaya, M.R., Sambashivan, S., Nelson, R., Ivanova, M.I., Sievers, S.A., Apostol, M.I., Thompson, M.J., Eisenberg, D., Atomic structures of amyloid cross-beta spines reveal varied steric zippers (2007) Nature, 447, pp. 453-457
Van Der Spoel, D., Lindahl, E., Hess, B., Groenhof, G., Mark, A.E., Berendsen, H.J., GROMACS: Fast, flexible, and free (2005) J. Comput. Chem, 26, pp. 1701-1718
Hess, B., Bekker, H., Berendsen, H.J.C., Fraaije, J., LINCS: A linear constraint solver for molecular simulations (1997) J. Comput. Chem, 18, pp. 1463-1472
Kaminski, G.A., Friesner, R.A., Tirado-Rives, J., Jorgensen, W.L., Evaluation and reparametrization of the OPLS-AA force field for proteins via comparison with accurate quantum chemical calculations on peptides (2001) J. Phys. Chem. B, 105, pp. 6474-6487
Humphrey, W., A. Dalke, and K. Schulten. 1996. VMD: visual molecular dynamics. J. Mol. Graph 14:33-38Kraulis, P.J., MOLSCRIPT:a program to produce both detailed and schematic plots of protein structures (1991) J. Appl. Cryst, 24, pp. 946-950
Perutz, M.F., Johnson, T., Suzuki, M., Finch, J.T., Glutamine repeats as polar zippers: Their possible role in inherited neurodegener- ative diseases (1994) Proc. Natl. Acad. Sci. USA, 91, pp. 5355-5358
Lawrence, M.C., Colman, P.M., Shape complementarity at protein/protein interfaces (1993) J. Mol. Biol, 234, pp. 946-950
Zheng, J., Ma, B., Tsai, C.J., Nussinov, R., Structural stability and dynamics of an amyloid-forming peptide GNNQQNY from the yeast prion sup-35 (2006) Biophys. J, 91, pp. 824-833
Fernandez, A., What factor drives the fibrillogenic association of beta-sheets? (2005) FEBS Lett, 579, pp. 6635-6640
Esposito, L., Pedone, C., Vitagliano, L., Molecular dynamics analyses of cross-beta-spine steric zipper models: Beta-sheet twisting and aggregation (2006) Proc. Natl. Acad. Sci. USA, 103, pp. 11533-11538
Perutz, M., Polar zippers: Their role in human disease (1994) Protein Sci, 3, pp. 1629-1637
Eberhardt, E.S., Raines, R.T., Amide-amide and amidewater hydrogen bonds: Implications for protein folding and stability (1994) J. Am. Chem. Soc, 116, pp. 2149-2150
Wu, C., Wang, Z., Lei, H., Zhang, W., Duan, Y., Dual binding modes of Congo red to amyloid protofibril surface observed in molecular dynamics simulations (2007) J. Am. Chem. Soc, 129, pp. 1225-1232
Tsemekhman, K., Goldschmidt, L., Eisenberg, D., Baker, D., Cooperative hydrogen bonding in amyloid formation (2007) Protein Sci, 16, pp. 761-764
Richardson, J.S., Richardson, D.C., Natural beta-sheet proteins use negative design to avoid edge-to-edge aggregation (2002) Proc. Natl. Acad. Sci. USA, 99, pp. 2754-2759
Laidman, J., Forse, G.J., Yeates, T.O., Conformational change and assembly through edge beta strands in transthyretin and other amyloid proteins (2006) Acc. Chem. Res, 39, pp. 576-583
Crick, S.L., Jayaraman, M., Frieden, C., Wetzel, R., Pappu, R.V., Fluorescence correlation spectroscopy shows that monomeric polyglutamine molecules form collapsed structures in aqueous solutions (2006) Proc. Natl. Acad. Sci. USA, 103, pp. 16764-16769
Insights into structure, stability, and toxicity of monomeric and aggregated polyglutamine models from molecular dynamics simulations
Nine genetically inherited neurodegenerative diseases are linked to abnormal expansions of a polyglutamine (polyQ) encoding region. Over the years, several structural models for polyQ regions have been proposed and confuted. The cross-beta-spine steric zipper motif, identified recently for the GNNQQNY peptide, represents an attractive model for amyloid fibers formed by polyQ fragments. Here we report a detailed molecular dynamics investigation of polyQ models assembled by cross-beta-spine steric zipper motifs. Our simulations indicate clearly that these assemblies are very stable. Glutamine side chains contribute strongly to the overall stability of the models by fitting perfectly within the zipper. In contrast to GNNQQNY zipper motifs, hydrogen bonding interactions provide a significant contribution to the overall stability of polyQ models. Molecular dynamics simulations carried out on monomeric polyQ forms (composed by 40-60 residues) show clearly that they can also assume structures stabilized by steric zipper motifs. Based on these findings, we build monomeric polyQ models that can explain recent data on the toxicity exerted by these species. In a more general context, our data suggests that polyQ models with interdigitated side chains can provide a structural rationale to several literature experiments on polyQ formation, stability, and toxicity.
Insights into structure, stability, and toxicity of monomeric and aggregated polyglutamine models from molecular dynamics simulations
Kállay C, Dávid A, Timári S, Nagy EM, Sanna D, Garribba E, Micera G, De Bona P, Pappalardo G, Rizzarelli E, Sóvágó I * Copper(II) complexes of rat amylin fragments(357 views) Dalton T (ISSN: 1477-9234, 1477-9226, 1477-9234electronic), 2011 Oct 14; 40(38): 9711-9721. Impact Factor:3.838 ViewExport to BibTeXExport to EndNote