EXAMINATION OF THE STRUCTURE OF THE TRANSTHYRETIN AMYLOID FIBRIL BY IMAGE-RECONSTRUCTION FROM ELECTRON-MICROGRAPHS

被引:127
作者
SERPELL, LC
SUNDE, M
FRASER, PE
LUTHER, PK
MORRIS, EP
SANGREN, O
LUNDGREN, E
BLAKE, CCF
机构
[1] UNIV TORONTO,CTR RES NEURODEGENERAT DIS,TORONTO,ON M5S 1A8,CANADA
[2] UNIV LONDON IMPERIAL COLL SCI & TECHNOL,BLACKETT LAB,BIOPHYS GRP,LONDON SW7 2BZ,ENGLAND
[3] UMEA UNIV,DEPT OPHTHALMOL,S-90187 UMEA,SWEDEN
[4] UMEA UNIV,DEPT CELL & MOLEC BIOL,S-90187 UMEA,SWEDEN
关键词
TRANSTHYRETIN; AMYLOID; ELECTRON MICROSCOPY; IMAGE RECONSTRUCTION; PROTOFILAMENT;
D O I
10.1006/jmbi.1995.0604
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Familial amyloidotic polyneuropathies are autosomal-dominant, inherited disorders that are characterised by the aggregation of variant proteins in a fibrillar form and by the extracellular deposition of amyloid fibrils. In familial amyloidotic polyneuropathy type I the protein constituent is a variant transthyretin molecule that has a Val to Met substitution at residue 30. Patients with this form of the disease present with sensory and motor disturbances, widespread autonomic dysfunction and in some cases, vitreous opacities. We have used amyloid material from the vitreous humours of patients homozygous for this mutation and analysed the structure of the fibrils by thin section electron microscopy and image reconstruction. Cross-sectional images of 200 different fibrils were collected and aligned, manually at first and then with an automated process that uses iterative cross-correlation. The averaged cross-section calculated produced a detailed view of the fibril substructure. The diameter of the fibrils is about 130 Angstrom. In cross-section they exhibit 4-fold symmetry with four proto-filaments, each measuring 40 to 50 Angstrom across, arranged around a central hollow core. (C) 1995 Academic Press Limited
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页码:113 / 118
页数:6
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