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Letter
Nature Structural Biology  9, 734 - 739 (2002)
Published online: 3 September 2002; | doi:10.1038/nsb838


There is an Erratum (January 2003) associated with this Letter.

Arrangement of subunits and ordering of bold beta-strands in an amyloid sheet

Ahmed A. Serag1, Christian Altenbach2, Mari Gingery3, Wayne L. Hubbell2 & Todd O. Yeates4

1  Molecular Biology Institute and School of Medicine, University of California, Los Angeles, California 90095, USA.

2  Jules Stein Eye Institute and Department of Chemistry and Biochemistry, University of California, Los Angeles, California 90095, USA.

3  Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, California 90095, USA.

4  Molecular Biology Institute, Department of Chemistry and Biochemistry, and Department of Energy, Laboratory of Structural Biology and Molecular Medicine, University of California, Los Angeles, California 90095, USA.

Correspondence should be addressed to Todd O. Yeates yeates@mbi.ucla.edu
Amyloid fibrils are associated with several disease states, but their structures have yet to be fully defined. Here we use site-directed spin labeling to explain some of the specific interactions that are formed between subunits when the protein transthyretin (TTR) assembles into amyloid fibrils, which are associated with both spontaneous and familial amyloid diseases in humans. The results suggest that fibrils are formed when a major conformational change displaces the terminal beta-strand from the edge of a beta-sheet in the native structure, exposing the penultimate strand. The newly exposed strand then allows a novel beta-sheet interaction to form between the TTR subunits. This interaction and another previously identified subunit association lead to a plausible model for the specific sequence of beta-strands in one of the indefinitely repeating beta-sheets of TTR amyloid, which is formed by a head-to-head, tail-to-tail arrangement of subunits.


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REFERENCE
Electron Paramagnetic Resonance (EPR) and Spin-labelling
Nature Encyclopaedia of Life Sciences

REVIEWS
THERAPEUTIC STRATEGIES FOR HUMAN AMYLOID DISEASES
Nature Reviews Drug Discovery Review Article (01 Apr 2002)

RESEARCH
Structure of the KcsA channel intracellular gate in the open state
Nature Structural Biology Letters (01 Oct 2001)
Structural insights into the early steps of receptor–transducer signal transfer in archaeal phototaxis
The EMBO Journal Article (01 Oct 2001)
A glimpse of a possible amyloidogenic intermediate of transthyretin
Nature Structural Biology Letters (01 Sep 2000)
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Nature Structural & Molecular Biology
ISSN: 1545-9993
EISSN: 1545-9985
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