1lds
From Proteopedia
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==Overview== | ==Overview== | ||
| - | Dissociation of human beta-2-microglobulin (beta(2)m) from the heavy chain | + | 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== | ==Disease== | ||
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[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Kalverda, A | + | [[Category: Kalverda, A P.]] |
| - | [[Category: Phillips, S | + | [[Category: Phillips, S E.V.]] |
| - | [[Category: Radford, S | + | [[Category: Radford, S E.]] |
| - | [[Category: Smith, D | + | [[Category: Smith, D P.]] |
| - | [[Category: Trinh, C | + | [[Category: Trinh, C H.]] |
[[Category: NA]] | [[Category: NA]] | ||
[[Category: immunoglobulin constant domain]] | [[Category: immunoglobulin constant domain]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:44:03 2008'' |
Revision as of 11:44, 21 February 2008
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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 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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