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Titolo:
Search for intermediate structures in transthyretin fibrillogenesis: Soluble tetrameric Tyr78Phe TTR expresses a specific epitope present only in amyloid fibrils
Autore:
Redondo, C; Damas, AM; Olofsson, A; Lundgren, E; Saraiva, MJM;
Indirizzi:
Univ Porto, Inst Mol & Cell Biol, Amyloid Unit, P-4150 Porto, Portugal Univ Porto Porto Portugal P-4150 l, Amyloid Unit, P-4150 Porto, Portugal Univ Porto, Inst Mol & Cell Biol, Mol Struct Unit, P-4150 Porto, Portugal Univ Porto Porto Portugal P-4150 Mol Struct Unit, P-4150 Porto, Portugal Univ Porto, Inst Ciencias Biomed Abel Salazar, P-4099003 Porto, Portugal Univ Porto Porto Portugal P-4099003 l Salazar, P-4099003 Porto, Portugal Umea Univ, Dept Cell & Mol Biol, S-90187 Umea, Sweden Umea Univ Umea Sweden S-90187 Dept Cell & Mol Biol, S-90187 Umea, Sweden
Titolo Testata:
JOURNAL OF MOLECULAR BIOLOGY
fascicolo: 3, volume: 304, anno: 2000,
pagine: 461 - 470
SICI:
0022-2836(200012)304:3<461:SFISIT>2.0.ZU;2-L
Fonte:
ISI
Lingua:
ENG
Soggetto:
POLYNEUROPATHY FAP; GENE-EXPRESSION; EVOLUTION; MUTANTS; PATHWAY;
Keywords:
transthyretin; amyloid; amyloid neuropathy; intermediates; epitopes;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
22
Recensione:
Indirizzi per estratti:
Indirizzo: Saraiva, MJM Univ Porto, Inst Mol & Cell Biol, Amyloid Unit, R Campo Alegre,N 823, P-4150 Porto, Portugal Univ Porto R Campo Alegre,N 823 Porto Portugal P-4150 rtugal
Citazione:
C. Redondo et al., "Search for intermediate structures in transthyretin fibrillogenesis: Soluble tetrameric Tyr78Phe TTR expresses a specific epitope present only in amyloid fibrils", J MOL BIOL, 304(3), 2000, pp. 461-470

Abstract

Familial Amyloidotic Polyneuropathy (FAP) is caused by the assembly of TTRinto an insoluble beta -sheet. The TTR tetramer is thought to dissociate into monomeric intermediates and subsequently polymerise into the pathogenicarnyloid form. The biochemical mechanism behind this transformation is unknown. We characterised intermediate TTR structures in the in vitro amyloidogenesis pathway by destabilising the AB loop through substitution of residue 78. Changes at this residue, should destabilise the TTR tetrameric fold, based on the known crystallographic structure of a Leu55Pro transthyretin variant. We generated a soluble tetrameric form of TTR that is recognised bya monoclonal antibody, previously reported to react only with highly amyloidogenic mutant proteins lacking the tetrameric native fold and with amyloid fibrils. BIAcore system analysis showed that Tyr78Phe had similar bindingproperties as synthetic fibrils. The affinity of this interaction was 10(7) M-1 We suggest that the tetrameric structure of Tyr78Phe is altered due to the loosening of the AB loops of the tetramer, leading to a structure that might represent an early intermediate in the fibrillogenesis pathway. (C)2000 Academic Press.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 05/04/20 alle ore 06:10:57