2f8o
From Proteopedia
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[[Image:2f8o.gif|left|200px]] | [[Image:2f8o.gif|left|200px]] | ||
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'''A Native to Amyloidogenic Transition Regulated by a Backbone Trigger''' | '''A Native to Amyloidogenic Transition Regulated by a Backbone Trigger''' | ||
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[[Category: Eakin, C M.]] | [[Category: Eakin, C M.]] | ||
[[Category: Miranker, A D.]] | [[Category: Miranker, A D.]] | ||
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| - | [[Category: | + | [[Category: Class-1 mhc]] |
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Revision as of 00:35, 4 May 2008
A Native to Amyloidogenic Transition Regulated by a Backbone Trigger
Contents |
Overview
Many polypeptides can self-associate into linear, aggregated assemblies termed amyloid fibers. High-resolution structural insights into the mechanism of fibrillogenesis are elusive owing to the transient and mixed oligomeric nature of assembly intermediates. Here, we report the conformational changes that initiate fiber formation by beta-2-microglobulin (beta2m) in dialysis-related amyloidosis. Access of beta2m to amyloidogenic conformations is catalyzed by selective binding of divalent cations. The chemical basis of this process was determined to be backbone isomerization of a conserved proline. On the basis of this finding, we designed a beta2m variant that closely adopts this intermediate state. The variant has kinetic, thermodynamic and catalytic properties consistent with its being a fibrillogenic intermediate of wild-type beta2m. Furthermore, it is stable and folded, enabling us to unambiguously determine the initiating conformational changes for amyloid assembly at atomic resolution.
Disease
Known disease associated with this structure: Hypoproteinemia, hypercatabolic OMIM:[109700]
About this Structure
2F8O is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
A native to amyloidogenic transition regulated by a backbone trigger., Eakin CM, Berman AJ, Miranker AD, Nat Struct Mol Biol. 2006 Mar;13(3):202-8. Epub 2006 Feb 19. PMID:16491088 Page seeded by OCA on Sun May 4 03:35:51 2008
