2q20

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{{Seed}}
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{{STRUCTURE_2q20| PDB=2q20 | SCENE= }}
{{STRUCTURE_2q20| PDB=2q20 | SCENE= }}
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'''Structure of the germline Vk1 O18/O8 light chain variable domain homodimer'''
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===Structure of the germline Vk1 O18/O8 light chain variable domain homodimer===
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==Overview==
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Amyloidoses are devastating and currently incurable diseases in which the process of amyloid formation causes fatal cellular and organ damage. The molecular mechanisms underlying amyloidoses are not well known. In this study, we address the structural basis of immunoglobulin light chain amyloidosis, which results from deposition of light chains produced by clonal plasma cells. We compare light chain amyloidosis protein AL-09 to its wild type counterpart, the kappaI O18/O8 light chain germline. Crystallographic studies indicate that both proteins form dimers. However, AL-09 has an altered dimer interface that is rotated 90 masculine from the kappaI O18/O8 dimer interface. The three non-conservative mutations in AL-09 are located within the dimer interface, consistent with their role in the decreased stability of this amyloidogenic protein. Moreover, AL-09 forms amyloid fibrils more quickly than kappaI O18/O8 in vitro. These results support the notion that the increased stability of the monomer and delayed fibril formation, together with a properly formed dimer, may be protective against amyloidogenesis. This could open a new direction into rational drug design for amyloidogenic proteins.
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The line below this paragraph, {{ABSTRACT_PUBMED_18400753}}, adds the Publication Abstract to the page
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(as it appears on PubMed at http://www.pubmed.gov), where 18400753 is the PubMed ID number.
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{{ABSTRACT_PUBMED_18400753}}
==About this Structure==
==About this Structure==
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[[Category: Protein fibril]]
[[Category: Protein fibril]]
[[Category: Vk1]]
[[Category: Vk1]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Apr 24 09:27:19 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 22:38:31 2008''

Revision as of 19:39, 28 July 2008

Image:2q20.png

Template:STRUCTURE 2q20

Structure of the germline Vk1 O18/O8 light chain variable domain homodimer

Template:ABSTRACT PUBMED 18400753

About this Structure

Full crystallographic information is available from OCA.

Reference

Altered dimer interface decreases stability in an amyloidogenic protein., Baden EM, Owen BA, Peterson FC, Volkman BF, Ramirez-Alvarado M, Thompson JR, J Biol Chem. 2008 Apr 8;. PMID:18400753

Page seeded by OCA on Mon Jul 28 22:38:31 2008

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