| Population of Nonnative States of Lysozyme Variants Drives Amyloid Fibril Formation. | |
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MedLine Citation:
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PMID: 21528861 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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The propensity of protein molecules to self-assemble into highly ordered, fibrillar aggregates lies at the heart of understanding many disorders ranging from Alzheimer's disease to systemic lysozyme amyloidosis. In this paper we use highly accurate kinetic measurements of amyloid fibril growth in combination with spectroscopic tools to quantify the effect of modifications in solution conditions and in the amino acid sequence of human lysozyme on its propensity to form amyloid fibrils under acidic conditions. We elucidate and quantify the correlation between the rate of amyloid growth and the population of nonnative states, and we show that changes in amyloidogenicity are almost entirely due to alterations in the stability of the native state, while other regions of the global free-energy surface remain largely unmodified. These results provide insight into the complex dynamics of a macromolecule on a multidimensional energy landscape and point the way for a better understanding of amyloid diseases. |
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Authors:
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Alexander K Buell; Anne Dhulesia; Maria F Mossuto; Nunilo Cremades; Janet R Kumita; Mireille Dumoulin; Mark E Welland; Tuomas P J Knowles; Xavier Salvatella; Christopher M Dobson |
Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-4-29 |
Journal Detail:
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Title: Journal of the American Chemical Society Volume: - ISSN: 1520-5126 ISO Abbreviation: - Publication Date: 2011 Apr |
Date Detail:
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Created Date: 2011-5-2 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 7503056 Medline TA: J Am Chem Soc Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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Nanoscience Centre, University of Cambridge , 11 JJ Thomson Avenue, Cambridge CB3 0FF, United Kingdom. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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