2f8o: Difference between revisions

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[[Image:2f8o.gif|left|200px]]
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{{STRUCTURE_2f8o|  PDB=2f8o  |  SCENE=  }}  
{{STRUCTURE_2f8o|  PDB=2f8o  |  SCENE=  }}  


'''A Native to Amyloidogenic Transition Regulated by a Backbone Trigger'''
===A Native to Amyloidogenic Transition Regulated by a Backbone Trigger===




==Overview==
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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.
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{{ABSTRACT_PUBMED_16491088}}


==Disease==
==Disease==
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[[Category: Beta-sandwich]]
[[Category: Beta-sandwich]]
[[Category: Class-1 mhc]]
[[Category: Class-1 mhc]]
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May  4 03:35:51 2008''
 
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 29 02:40:32 2008''

Revision as of 02:40, 29 July 2008

File:2f8o.png

Template:STRUCTURE 2f8o

A Native to Amyloidogenic Transition Regulated by a Backbone TriggerA Native to Amyloidogenic Transition Regulated by a Backbone Trigger

Template:ABSTRACT PUBMED 16491088

DiseaseDisease

Known disease associated with this structure: Hypoproteinemia, hypercatabolic OMIM:[109700]

About this StructureAbout this Structure

2F8O is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

ReferenceReference

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 Tue Jul 29 02:40:32 2008

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