4FXL

Crystal structure of the D76N Beta-2 Microglobulin mutant

4FXL の概要

• エントリーDOI: 10.2210/pdb4fxl/pdb
• 分子名称: Beta-2-microglobulin, SODIUM ION, ACETATE ION, ... (5 entities in total)
• 機能のキーワード: immunoglobin, beta-sandwitch, amyloidosis, pathologic mutation, genetic disease, mhc class i, 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: 12066.53

構造登録者

Ricagno, S.,Bellotti, V.,Pepys, M.B.,Stoppini, M.,Bolognesi, M. (登録日: 2012-07-03, 公開日: 2012-08-15, 最終更新日: 2024-11-27)

主引用文献

Valleix, S.,Gillmore, J.D.,Bridoux, F.,Mangione, P.P.,Dogan, A.,Nedelec, B.,Boimard, M.,Touchard, G.,Goujon, J.M.,Lacombe, C.,Lozeron, P.,Adams, D.,Lacroix, C.,Maisonobe, T.,Plante-Bordeneuve, V.,Vrana, J.A.,Theis, J.D.,Giorgetti, S.,Porcari, R.,Ricagno, S.,Bolognesi, M.,Stoppini, M.,Delpech, M.,Pepys, M.B.,Hawkins, P.N.,Bellotti, V.
Hereditary systemic amyloidosis due to Asp76Asn variant beta-2-microglobulin.
N.Engl.J.Med., 366:2276-2283, 2012

PubMed Abstract: We describe a kindred with slowly progressive gastrointestinal symptoms and autonomic neuropathy caused by autosomal dominant, hereditary systemic amyloidosis. The amyloid consists of Asp76Asn variant β(2)-microglobulin. Unlike patients with dialysis-related amyloidosis caused by sustained high plasma concentrations of wild-type β(2)-microglobulin, the affected members of this kindred had normal renal function and normal circulating β(2)-microglobulin values. The Asp76Asn β(2)-microglobulin variant was thermodynamically unstable and remarkably fibrillogenic in vitro under physiological conditions. Previous studies of β(2)-microglobulin aggregation have not shown such amyloidogenicity for single-residue substitutions. Comprehensive biophysical characterization of the β(2)-microglobulin variant, including its 1.40-Å, three-dimensional structure, should allow further elucidation of fibrillogenesis and protein misfolding.

PubMed: 22693999
DOI: 10.1056/NEJMoa1201356

実験手法

X-RAY DIFFRACTION (1.4 Å)