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Examination of the structure of the transthyretin amyloid fibril by image reconstruction from electron micrographs

journal contribution
posted on 2023-06-08, 08:40 authored by Louise SerpellLouise Serpell, M Sunde, P E Fraser, P K Luther, E P Morris, O Sangren, E Lundgren, C C F Blake
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 Å. In cross-section they exhibit 4-fold symmetry with four proto-filaments, each measuring 40 to 50 Å across, arranged around a central hollow core.

History

Publication status

  • Published

Journal

Journal of Molecular Biology

ISSN

00222836

Issue

2

Volume

254

Page range

113-118

Department affiliated with

  • Biochemistry Publications

Full text available

  • No

Peer reviewed?

  • Yes

Legacy Posted Date

2012-02-06

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