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Journal home Advance online publication Current issue Archive Press releases Supplements Focus Guide to authors Online submission Permissions For referees Free online issue Contact the journal Subscribe Advertising work@npg naturereprints About this site For librarians   NPG Resources Nature Nature Cell Biology Nature Reviews Molecular Cell Biology The EMBO Journal Nature Reports Avian Flu NPG Subject areas Biotechnology Cancer Chemistry Clinical Medicine Dentistry Development Drug Discovery Earth Sciences Evolution & Ecology Genetics Immunology Materials Science Medical Research Microbiology Molecular Cell Biology Neuroscience Pharmacology Physics Browse all publications 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 -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.eduAmyloid 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 -strand from the edge of a -sheet in the native structure, exposing the penultimate strand. The newly exposed strand then allows a novel -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 -strands in one of the indefinitely repeating -sheets of TTR amyloid, which is formed by a head-to-head, tail-to-tail arrangement of subunits. MORE ARTICLES LIKE THIS These links to content published by NPG are automatically generated 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)  See all 11 matches for Research  Top Abstract Previous | Next Table of contents Full text Download PDF Send to a friend Save this link Open Innovation Challenges Single-cell Analysis Platform Deadline: Dec 02 2009 Reward: $5,000 USD This Challenge is looking for novel approaches to analyzing changes at a single-cell level. This is... Novel Approaches to Protecting Maize from Insect Damage Deadline: Jan 31 2010 Reward: $20,000 USD The Seeker is looking for novel approaches to protecting maize from insect damage. This Challenge re... More Challenges Powered by: nature jobs Research Assistant / Associate University of Glasgow Glasgow, UK Bioprocess Engineer Praj Matrix - Praj Industries Ltd Pune, Maharashtra Pune-411021 India More science jobs Post a job for free Figures & Tables Export citation Search buyers guide:   ADVERTISEMENT

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