2Z9T

Crystal structure of the human beta-2 microglobulin mutant W60G

2Z9T の概要

• エントリーDOI: 10.2210/pdb2z9t/pdb
• 分子名称: Beta-2-microglobulin (2 entities in total)
• 機能のキーワード: beta-2-microglobulin, tryptophan, glycine, amyloidosis, dra, beta fibrils, disease mutation, glycation, glycoprotein, immune response, immunoglobulin domain, mhc i, pyrrolidone carboxylic acid, secreted, immune system
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Secreted: P61769
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 11750.20

構造登録者

Ricagno, S.,Bolognesi, M.,Bellotti, V.,Corazza, A.,Rennella, E.,Gural, D.,Mimmi, M.C.,Betto, E.,Pucillo, C.,Fogolari, F.,Viglino, P.,Raimondi, S.,Giorgetti, S.,Bolognesi, B.,Merlini, G.,Stoppini, M. (登録日: 2007-09-26, 公開日: 2008-04-22, 最終更新日: 2024-11-13)

主引用文献

Esposito, G.,Ricagno, S.,Corazza, A.,Rennella, E.,Gumral, D.,Mimmi, M.C.,Betto, E.,Pucillo, C.E.M.,Fogolari, F.,Viglino, P.,Raimondi, S.,Giorgetti, S.,Bolognesi, B.,Merlini, G.,Stoppini, M.,Bolognesi, M.,Bellotti, V.
The controlling roles of Trp60 and Trp95 in beta2-microglobulin function, folding and amyloid aggregation properties
J.Mol.Biol., 378:885-895, 2008

PubMed Abstract: 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-->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-->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.

PubMed: 18395224
DOI: 10.1016/j.jmb.2008.03.002

実験手法

X-RAY DIFFRACTION (1.8 Å)