1py4

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{{STRUCTURE_1py4| PDB=1py4 | SCENE= }}
{{STRUCTURE_1py4| PDB=1py4 | SCENE= }}
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'''Beta2 microglobulin mutant H31Y displays hints for amyloid formations'''
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===Beta2 microglobulin mutant H31Y displays hints for amyloid formations===
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==Overview==
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beta2-Microglobulin (beta2m) is the non-covalently bound light chain of the human class I major histocompatibility complex (MHC-I). The natural turnover of MHC-I gives rise to the release of beta2m into plasmatic fluids and to its catabolism in the kidney. beta2m dissociation from the heavy chain of the complex is a severe complication in patients receiving prolonged hemodialysis. As a consequence of renal failure, the increasing beta2m concentrations can lead to deposition of the protein as amyloid fibrils. Here we characterize the His31--&gt;Tyr human beta2m mutant, a non-natural form of beta2m that is more stable than the wild-type protein, displaying a ten-fold acceleration of the slow phase of folding. We report the 2.9A resolution crystal structure and the NMR characterization of the mutant beta2m, focussing on selected structural features and on the molecular packing observed in the crystals. Juxtaposition of the four mutant beta2m molecules contained in the crystal asymmetric unit, and specific hydrogen bonds, stabilize a compact protein assembly. Conformational heterogeneity of the four independent molecules, some of their mutual interactions and partial unpairing of the N-terminal beta-strand in one protomer are in keeping with the amyloidogenic properties displayed by the mutant beta2m.
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(as it appears on PubMed at http://www.pubmed.gov), where 14698299 is the PubMed ID number.
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{{ABSTRACT_PUBMED_14698299}}
==Disease==
==Disease==
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[[Category: Dialysis related amyloidosis]]
[[Category: Dialysis related amyloidosis]]
[[Category: Protein mutant]]
[[Category: Protein mutant]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 05:38:02 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 14:34:53 2008''

Revision as of 11:34, 28 July 2008

Image:1py4.png

Template:STRUCTURE 1py4

Contents

Beta2 microglobulin mutant H31Y displays hints for amyloid formations

Template:ABSTRACT PUBMED 14698299

Disease

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

About this Structure

1PY4 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

Reference

beta2-microglobulin H31Y variant 3D structure highlights the protein natural propensity towards intermolecular aggregation., Rosano C, Zuccotti S, Mangione P, Giorgetti S, Bellotti V, Pettirossi F, Corazza A, Viglino P, Esposito G, Bolognesi M, J Mol Biol. 2004 Jan 23;335(4):1051-64. PMID:14698299

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