1PY4

Beta2 microglobulin mutant H31Y displays hints for amyloid formations

1PY4 の概要

• エントリーDOI: 10.2210/pdb1py4/pdb
• 分子名称: Beta-2-microglobulin precursor (2 entities in total)
• 機能のキーワード: amyloid, dialysis related amyloidosis, c-type immunoglobulin, protein mutant, signaling protein
• 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: 4
• 化学式量合計: 47617.53

構造登録者

Rosano, C.,Zuccotti, S.,Mangione, P.,Giorgetti, S.,Bellotti, V.,Pettirossi, F.,Corazza, A.,Viglino, P.,Esposito, G.,Bolognesi, M. (登録日: 2003-07-08, 公開日: 2004-05-04, 最終更新日: 2024-11-20)

主引用文献

Rosano, C.,Zuccotti, S.,Mangione, P.,Giorgetti, S.,Bellotti, V.,Pettirossi, F.,Corazza, A.,Viglino, P.,Esposito, G.,Bolognesi, M.
beta2-microglobulin H31Y variant 3D structure highlights the protein natural propensity towards intermolecular aggregation
J.Mol.Biol., 335:1051-1064, 2004

PubMed Abstract: 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-->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.

PubMed: 14698299
DOI: 10.1016/j.jmb.2003.11.040

実験手法

X-RAY DIFFRACTION (2.9 Å)