1lds
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(New page: 200px<br /> <applet load="1lds" size="450" color="white" frame="true" align="right" spinBox="true" caption="1lds, resolution 1.80Å" /> '''Crystal Structure o...)
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Revision as of 15:52, 12 November 2007
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Crystal Structure of monomeric human beta-2-microglobulin
Contents |
Overview
Dissociation of human beta-2-microglobulin (beta(2)m) from the heavy chain, of the class I HLA complex is a critical first step in the formation of, amyloid fibrils from this protein. As a consequence of renal failure, the, concentration of circulating monomeric beta(2)m increases, ultimately, leading to deposition of the protein into amyloid fibrils and development, of the disorder, dialysis-related amyloidosis. Here we present the crystal, structure of a monomeric form of human beta(2)m determined at 1.8-A, resolution that reveals remarkable structural changes relative to the, HLA-bound protein. These involve the restructuring of a beta bulge that, separates two short beta strands to form a new six-residue beta strand at, one edge of this beta sandwich protein. These structural changes remove, key features proposed to have evolved to protect beta sheet proteins from, aggregation [Richardson, J. & Richardson, D. (2002) Proc. Natl. Acad. Sci., USA 99, 2754-2759] and replaces them with an aggregation-competent, surface. In combination with solution studies using (1)H NMR, we show that, the crystal structure presented here represents a rare species in solution, that could provide important clues about the mechanism of amyloid, formation from the normally highly soluble native protein.
Disease
Known disease associated with this structure: Hypoproteinemia, hypercatabolic OMIM:[109700]
About this Structure
1LDS is a Single protein structure of sequence from Homo sapiens with NA as ligand. Full crystallographic information is available from OCA.
Reference
Crystal structure of monomeric human beta-2-microglobulin reveals clues to its amyloidogenic properties., Trinh CH, Smith DP, Kalverda AP, Phillips SE, Radford SE, Proc Natl Acad Sci U S A. 2002 Jul 23;99(15):9771-6. Epub 2002 Jul 15. PMID:12119416
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