Functional analysis of melanocortin-4-receptor mutants identified in severely obese subjects living in Southern Italy (752 views)
Gene (ISSN: 0378-1119), 2010 Jun 1; 457(1-2): 35-41.
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Paper type: Journal Article,
Impact factor: 2.266, 5-year impact factor: 2.61
Url: http://www.scopus.com/inward/record.url?eid=2-s2.0-77951935284&partnerID=40&md5=2ef0d08518837a7e477974e56b94d106
Keywords: Confocal Microscopy, Dominant Negative, Functional Analysis, Homology Modeling, Mc4r Mutants, Severe Obesity, Melanocortin 4 Receptor, Alpha Intermedin, Ligand, Mc4r Protein, Human, Mitogen Activated Protein Kinase 1, Mutant Protein, Adult, Amino Acid Substitution, Amino Terminal Sequence, Article, Carboxy Terminal Sequence, Cell Membrane, Cell Mutant, Cellular Distribution, Child, Controlled Study, Disease Severity, Endoplasmic Reticulum, Gene Identification, Genetic Association, Heterozygosity, Homeostasis, Homozygosity, Human Cell, Italy, Ligand Binding, Major Clinical Study, Missense Mutation, Priority Journal, Protein Analysis, Protein Function, Signal Transduction, Structural Homology, Structure Analysis, Wild Type, Cell Culture, Chemical Structure, Drug Effect, Genetic Transfection, Metabolism, Morbid Obesity, Phosphorylation, Physiology, Protein Binding, Structure Activity Relation, Tissue Distribution, Alpha-Msh, Mitogen-Activated Protein Kinase 1, Molecular, Structure-Activity Relationship,
Affiliations:
*** IBB - CNR ***
Dipartimento di Studi delle Istituzioni e dei Sistemi Territoriali, Facoltà di Scienze Motorie, Università Parthenope, Naples, Italy
Istituto di Ricovero e Cura a carattere scientifico, Fondazione SDN, Naples, Italy
Dipartimento di Medicina Clinica e Sperimentale, Università di Napoli Federico II, Naples, Italy
CNR Istituto di Endocrinologia ed Oncologia Sperimentale G. Salvatore, Università di Napoli Federico II, Naples, Italy
CNR Istituto di Biostrutture e Bioimmagini, Naples, Italy
Dipartimento Scienze per la Salute, Università del Molise, Campobasso, Italy
CEINGE-Biotecnologie Avanzate s.ca.r.l., Naples, Italy
Dipartimento di Biochimica e Biotecnologie Mediche, Università Federico II, Naples, Italy
References:
Not available.
Gene (ISSN: 0378-1119), 2010 Jun 1; 457(1-2): 35-41.
Export to BibTeX Export to EndNote
Paper type: Journal Article,
Impact factor: 2.266, 5-year impact factor: 2.61
Url: http://www.scopus.com/inward/record.url?eid=2-s2.0-77951935284&partnerID=40&md5=2ef0d08518837a7e477974e56b94d106
Keywords: Confocal Microscopy, Dominant Negative, Functional Analysis, Homology Modeling, Mc4r Mutants, Severe Obesity, Melanocortin 4 Receptor, Alpha Intermedin, Ligand, Mc4r Protein, Human, Mitogen Activated Protein Kinase 1, Mutant Protein, Adult, Amino Acid Substitution, Amino Terminal Sequence, Article, Carboxy Terminal Sequence, Cell Membrane, Cell Mutant, Cellular Distribution, Child, Controlled Study, Disease Severity, Endoplasmic Reticulum, Gene Identification, Genetic Association, Heterozygosity, Homeostasis, Homozygosity, Human Cell, Italy, Ligand Binding, Major Clinical Study, Missense Mutation, Priority Journal, Protein Analysis, Protein Function, Signal Transduction, Structural Homology, Structure Analysis, Wild Type, Cell Culture, Chemical Structure, Drug Effect, Genetic Transfection, Metabolism, Morbid Obesity, Phosphorylation, Physiology, Protein Binding, Structure Activity Relation, Tissue Distribution, Alpha-Msh, Mitogen-Activated Protein Kinase 1, Molecular, Structure-Activity Relationship,
Affiliations:
*** IBB - CNR ***
Dipartimento di Studi delle Istituzioni e dei Sistemi Territoriali, Facoltà di Scienze Motorie, Università Parthenope, Naples, Italy
Istituto di Ricovero e Cura a carattere scientifico, Fondazione SDN, Naples, Italy
Dipartimento di Medicina Clinica e Sperimentale, Università di Napoli Federico II, Naples, Italy
CNR Istituto di Endocrinologia ed Oncologia Sperimentale G. Salvatore, Università di Napoli Federico II, Naples, Italy
CNR Istituto di Biostrutture e Bioimmagini, Naples, Italy
Dipartimento Scienze per la Salute, Università del Molise, Campobasso, Italy
CEINGE-Biotecnologie Avanzate s.ca.r.l., Naples, Italy
Dipartimento di Biochimica e Biotecnologie Mediche, Università Federico II, Naples, Italy
References:
Not available.
Functional analysis of melanocortin-4-receptor mutants identified in severely obese subjects living in Southern Italy
The melanocortin-4 receptor (MC4R) is involved in regulating energy homeostasis; mutations in this gene have been associated with 1-5% of early-onset human obesity. The aim of this study was to functionally characterize MC4R mutations identified in morbidly obese subjects living in Southern Italy. We studied their ligand binding, signaling pathway and subcellular localization. As expected, mutants Q43X and S19fsX51, which produce truncated forms of receptor, were devoid of activity. The activity of mutants W174C and A175T were very different even though the mutations are adjacent and are in the same transmembrane helix (TMH). In fact, the production and expression of mutant A175T on the plasma-membrane (PM) was similar to that of the wild-type (wt) receptor and the mutant retained 70% of wt receptor activity; on the contrary, the production of W174C mutant in the cytoplasm was similar to that of the wt receptor and mutant A175T but was only barely detectable on the PM and was devoid of activity. Confocal microscopy showed that W174C remained entrapped in the endoplasmic reticulum (ER) of the cells. Structural analysis showed that substitution of Trp174, located in the middle of TMH4 and 100% conserved in all known MC4Rs, with Cys could impair the relative orientation of TMH2 and TMH4 thereby affecting the overall protein architecture. Furthermore, co-expression studies showed that mutant A175T but not W174C had a dominant negative effect on the wt receptor activity. (C) 2010 Elsevier B.V. All rights reserved.
The melanocortin-4 receptor (MC4R) is involved in regulating energy homeostasis; mutations in this gene have been associated with 1-5% of early-onset human obesity. The aim of this study was to functionally characterize MC4R mutations identified in morbidly obese subjects living in Southern Italy. We studied their ligand binding, signaling pathway and subcellular localization. As expected, mutants Q43X and S19fsX51, which produce truncated forms of receptor, were devoid of activity. The activity of mutants W174C and A175T were very different even though the mutations are adjacent and are in the same transmembrane helix (TMH). In fact, the production and expression of mutant A175T on the plasma-membrane (PM) was similar to that of the wild-type (wt) receptor and the mutant retained 70% of wt receptor activity; on the contrary, the production of W174C mutant in the cytoplasm was similar to that of the wt receptor and mutant A175T but was only barely detectable on the PM and was devoid of activity. Confocal microscopy showed that W174C remained entrapped in the endoplasmic reticulum (ER) of the cells. Structural analysis showed that substitution of Trp174, located in the middle of TMH4 and 100% conserved in all known MC4Rs, with Cys could impair the relative orientation of TMH2 and TMH4 thereby affecting the overall protein architecture. Furthermore, co-expression studies showed that mutant A175T but not W174C had a dominant negative effect on the wt receptor activity. (C) 2010 Elsevier B.V. All rights reserved.
Functional analysis of melanocortin-4-receptor mutants identified in severely obese subjects living in Southern Italy
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Functional analysis of melanocortin-4-receptor mutants identified in severely obese subjects living in Southern Italy
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Impact Factor: 3.447
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Giuffrida ML, Rizzarelli E, Tomaselli GA, Satriano C, Trusso Sfrazzetto G
* A novel fully water-soluble Cu(i) probe for fluorescence live cell imaging (854 views)
Chem Commun (ISSN: 1359-7345, 1364-548x, 1364-548xelectronic), 2014; 50(69): 9835-9838.
Impact Factor: 6.834
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Satriano C, Sfrazzetto GT, Amato ME, Ballistreri FP, Copani A, Giuffrida ML, Grasso G, Pappalardo A, Rizzarelli E, Tomaselli GA, Toscano RM
* A ratiometric naphthalimide sensor for live cell imaging of copper(i) (861 views)
Chem Commun (ISSN: 1359-7345, 1364-548x, 1364-548xelectronic), 2013 Jun 21; 49(49): 5565-5567.
Impact Factor: 6.718
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Scudiero O, Galdiero S, Nigro E, Del Vecchio L, Di Noto R, Cantisani M, Colavita I, Galdiero M, Cassiman JJ, Daniele A, Pedone C, Salvatore F
* Chimeric beta-defensin analogs, including the novel 3NI analog, display salt-resistant antimicrobial activity and lack toxicity in human epithelial cell lines (897 views)
Antimicrob Agents Ch (ISSN: 1098-6596, 0066-4804), 2013 Apr; 57(4): 1701-1708.
Impact Factor: 4.451
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Scalia M, Satriano C, Greca R, Stella AM, Rizzarelli E, Spina-Purrello V
* PARP-1 inhibitors DPQ and PJ-34 negatively modulate proinflammatory commitment of human glioblastoma cells (904 views)
Neurochemical Research (ISSN: 1573-6903, 0364-3190), 2013 Jan; 38(1): 50-58.
Impact Factor: 2.551
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Smaldone G, Falanga A, Capasso D, Guarnieri D, Correale S, Galdiero M, Netti PA, Zollo M, Galdiero S, Di Gaetano S, Pedone E
* gH625 is a viral derived peptide for effective delivery of intrinsically disordered proteins (852 views)
Int J Nanomed (ISSN: 1178-2013, 1176-9114, 1178-2013electronic), 2013; 8: 2555-2565.
Impact Factor: 4.195
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Scarí G, Porta F, Fascio U, Avvakumova S, Dal Santo V, De Simone M, Saviano M, Leone M, Del Gatto A, Pedone C, Zaccaro L
* Gold nanoparticles capped by a GC-containing peptide functionalized with an RGD motif for integrin targeting (1027 views)
Bioconjug Chem (ISSN: 1520-4812, 1043-1802, 1520-4812electronic), 2012 Mar 21; 23(3): 340-349.
Impact Factor: 4.58
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Tarallo R, Accardo A, Falanga A, Guarnieri D, Vitiello G, Netti P, D'Errico G, Morelli G, Galdiero S
* Clickable functionalization of liposomes with the gH625 peptide from herpes simplex virus type i for intracellular drug delivery (987 views)
Chemistry (ISSN: 0947-6539, 1521-3765, 1521-3765electronic), 2011 Nov 4; 17(45): 12659-12668.
Impact Factor: 5.925
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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 (825 views)
Biopolymers (ISSN: 0006-3525, 0006-6352, 0006-3525print), 2010 Nov; 93(11): 1011-1021.
Impact Factor: 2.572
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Palmieri C, Falcone C, Iaccino E, Tuccillo FM, Gaspari M, Trimboli F, De Laurentiis A, Luberto L, Pontoriero M, Pisano A, Vecchio E, Fierro O, Panico M, Larobina M, Gargiulo S, Costa N, Dal Piaz F, Schiavone M, Arra C, Giudice A, Palma G, Barbieri A, Quinto I, Scala G
* In vivo targeting and growth inhibition of the A20 murine B-cell lymphoma by an idiotype-specific peptide binder (1065 views)
Blood (ISSN: 0006-4971, 0006-6497, 0390-6078), 2010 Jul 15; 116(2): 226-238.
Impact Factor: 10.558
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Daniele A, Scala I, Cardillo G, Pennino C, Ungaro C, Sibilio M, Parenti G, Esposito L, Zagari A, Andria G, Salvatore F
* Functional and structural characterization of novel mutations and genotype-phenotype correlation in 51 phenylalanine hydroxylase deficient families from Southern Italy (865 views)
Febs Journal (ISSN: 1742-464x), 2009 Apr; 276(7): 2048-2059.
Impact Factor: 3.042
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Francalanci F, Avolio M, De Luca E, Longo DL, Menchise V, Guazzi P, Sgro F, Marino M, Goitre L, Balzac F, Trabalzini L, Retta SF
* Structural and functional differences between KRIT1A and KRIT1B isoforms: A framework for understanding CCM pathogenesis (857 views)
Exp Cell Res (ISSN: 0014-4827), 2009 Jan 15; 315(2): 285-303.
Impact Factor: 3.589
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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 (631 views)
J Proteome Res (ISSN: 1535-3893), 2009 Jan; 8(1): 327-334.
Impact Factor: 5.132
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Pentimalli F, Palmieri D, Pacelli R, Garbi C, Cesari R, Martin E, Pierantoni GM, Chieffi P, Croce CM, Costanzo V, Fedele M, Fusco A
* HMGA1 protein is a novel target of the ATM kinase (892 views)
European Journal Of Cancer (ISSN: 0959-8049), 2008 Nov; 44(17): 2668-2679.
Impact Factor: 4.475
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Daniele A, Cardillo G, Pennino C, Carbone MT, Scognamiglio D, Esposito L, Correra A, Castaldo G, Zagari A, Salvatore F
* Five human phenylalanine hydroxylase proteins identified in mild hyperphenylalaninemia patients are disease-causing variants (676 views)
Bba-Gen Subjects (ISSN: 0925-4439, 0006-3002, 1570-9639), 2008 Jun; 1782(6): 378-384.
Impact Factor: 2.233
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Guarnieri D, Borzacchiello A, De Capua A, Ruvo M, Netti P
* Engineering of covalently immobilized gradients of RGD peptides on hydrogel scaffolds: Effect on cell behaviour (823 views)
Macromol Sympos (ISSN: 1022-1360), 2008; 266(1): 36-40.
Impact Factor: 0
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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 (1522 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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Pedone E, D'Ambrosio K, De Simone G, Rossi M, Pedone C, Bartolucci S
* Insights on a new PDI-like family: Structural and functional analysis of a protein disulfide oxidoreductase from the bacterium Aquifex aeolicus (815 views)
J Mol Biol (ISSN: 0022-2836, 1089-8638, 1089-8638electronic), 2006 Feb 10; 356(1): 155-164.
Impact Factor: 4.89
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Esposito G, Vitagliano L, Santamaria R, Viola A, Zagari A, Salvatore F
* Structural and functional analysis of aldolase B mutants related to hereditary fructose intolerance (581 views)
Febs Lett (ISSN: 0014-5793, 0014-5793print, 1873-3468electronic), 2002 Nov 6; 531(2): 152-156.
Impact Factor: 3.912
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33 Records (32 excluding Abstracts).
Total impact factor: 149.096 (145.862 excluding Abstracts).
Total 5 year impact factor: 140.133 (136.431 excluding Abstracts).
Total impact factor: 149.096 (145.862 excluding Abstracts).
Total 5 year impact factor: 140.133 (136.431 excluding Abstracts).
752 views. Last view on Tuesday 29 April 2025, 5:06:50
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