2z9t

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{{STRUCTURE_2z9t| PDB=2z9t | SCENE= }}
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'''Crystal structure of the human beta-2 microglobulin mutant W60G'''
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===Crystal structure of the human beta-2 microglobulin mutant W60G===
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==Overview==
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Amyloidosis associated to hemodialysis is caused by persistently high beta(2)-microglobulin (beta(2)m) serum levels. beta(2)m is an intrinsically amyloidogenic protein whose capacity to assemble into amyloid fibrils in vitro and in vivo is concentration dependent; no beta(2)m genetic variant is known in the human population. We investigated the roles of two evolutionary conserved Trp residues in relation to beta(2)m structure, function and folding/misfolding by means of a combined biophysical and functional approach. We show that Trp60 plays a functional role in promoting the association of beta(2)m in class I major histocompatibility complex; it is exposed to the solvent at the apex of a protein loop in order to accomplish such function. The Trp60--&gt;Gly mutation has a threefold effect: it stabilizes beta(2)m, inhibits beta(2)m amyloidogenic propensity and weakens the interaction with the class I major histocompatibility complex heavy chain. On the contrary, Trp95 is buried in the beta(2)m core; the Trp95--&gt;Gly mutation destabilizes the protein, which is unfolded in solution, yielding nonfibrillar beta(2)m aggregates. Trp60 and Trp95 therefore play differential and complementary roles in beta(2)m, being relevant for function (Trp60) and for maintenance of a properly folded structure (Trp95) while affecting in distinct ways the intrinsic propensity of wild-type beta(2)m towards self-aggregation into amyloid fibrils.
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(as it appears on PubMed at http://www.pubmed.gov), where 18395224 is the PubMed ID number.
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{{ABSTRACT_PUBMED_18395224}}
==About this Structure==
==About this Structure==
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[[Category: Secreted]]
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[[Category: Tryptophan]]
[[Category: Tryptophan]]
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Revision as of 03:02, 29 July 2008

Template:STRUCTURE 2z9t

Crystal structure of the human beta-2 microglobulin mutant W60G

Template:ABSTRACT PUBMED 18395224

About this Structure

2Z9T is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

Reference

The controlling roles of Trp60 and Trp95 in beta2-microglobulin function, folding and amyloid aggregation properties., Esposito G, Ricagno S, Corazza A, Rennella E, Gumral D, Mimmi MC, Betto E, Pucillo CE, Fogolari F, Viglino P, Raimondi S, Giorgetti S, Bolognesi B, Merlini G, Stoppini M, Bolognesi M, Bellotti V, J Mol Biol. 2008 May 9;378(4):885-95. Epub 2008 Mar 8. PMID:18395224

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