2d4f
From Proteopedia
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'''The Crystal Structure of human beta2-microglobulin''' | '''The Crystal Structure of human beta2-microglobulin''' | ||
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[[Category: Matsuura, T.]] | [[Category: Matsuura, T.]] | ||
[[Category: Nakagawa, A.]] | [[Category: Nakagawa, A.]] | ||
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Revision as of 20:41, 3 May 2008
The Crystal Structure of human beta2-microglobulin
Overview
Beta2-microglobulin (beta2-m), a protein responsible for dialysis-related amyloidosis, adopts an immunoglobulin domain fold in its native state. Although beta2-m has Trp residues at positions 60 and 95, both are located near the surface of the domain. Hence, beta2-m does not have a conserved Trp common to other immunoglobulin domains, which is buried in close proximity to the disulfide bond. To study the structure of amyloid fibrils in relation to their native fold, we prepared a series of Trp mutants. Trp60 and Trp95 were both replaced with Phe, and a single Trp was introduced at various positions. Among various mutants, W39-beta2-m, in which a Trp was introduced at the position corresponding to the conserved Trp, exhibited a remarkable quenching of fluorescence in the native state, as observed for other immunoglobulin domains. An x-ray structural analysis revealed that W39-beta2-m assumes the native fold with Trp39 located in the vicinity of the disulfide bond. Comparison of the fluorescence spectra of various mutants for the native and fibrillar forms indicated that, while the Trp residues introduced in the middle of the beta2-m sequence tend to be buried in the fibrils, those located in the C-terminal region are more exposed. In addition, the fluorescence spectra of fibrils prepared at pH 2.5 and 7.0 revealed a large difference in the fluorescence intensity for W60-beta2-m, implying a major structural difference between them.
About this Structure
2D4F is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Conformation of amyloid fibrils of beta2-microglobulin probed by tryptophan mutagenesis., Kihara M, Chatani E, Iwata K, Yamamoto K, Matsuura T, Nakagawa A, Naiki H, Goto Y, J Biol Chem. 2006 Oct 13;281(41):31061-9. Epub 2006 Aug 10. PMID:16901902 Page seeded by OCA on Sat May 3 23:41:16 2008