5CS7

The crystal structure of wt beta2-microglobulin at room temperature

5CS7 の概要

• エントリーDOI: 10.2210/pdb5cs7/pdb
• 関連するPDBエントリー: 2YXF
• 分子名称: Beta-2-microglobulin (2 entities in total)
• 機能のキーワード: beta-2 microglobulin, amyloidosis, room temperature, immunoglobulin-like, immune system
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 11879.36

構造登録者

de Rosa, M.,Mota, C.S.,de Sanctis, D.,Bolognesi, M.,Ricagno, S. (登録日: 2015-07-23, 公開日: 2016-08-10, 最終更新日: 2024-10-23)

主引用文献

Le Marchand, T.,de Rosa, M.,Salvi, N.,Sala, B.M.,Andreas, L.B.,Barbet-Massin, E.,Sormanni, P.,Barbiroli, A.,Porcari, R.,Sousa Mota, C.,de Sanctis, D.,Bolognesi, M.,Emsley, L.,Bellotti, V.,Blackledge, M.,Camilloni, C.,Pintacuda, G.,Ricagno, S.
Conformational dynamics in crystals reveal the molecular bases for D76N beta-2 microglobulin aggregation propensity.
Nat Commun, 9:1658-1658, 2018

PubMed Abstract: Spontaneous aggregation of folded and soluble native proteins in vivo is still a poorly understood process. A prototypic example is the D76N mutant of beta-2 microglobulin (β2m) that displays an aggressive aggregation propensity. Here we investigate the dynamics of β2m by X-ray crystallography, solid-state NMR, and molecular dynamics simulations to unveil the effects of the D76N mutation. Taken together, our data highlight the presence of minor disordered substates in crystalline β2m. The destabilization of the outer strands of D76N β2m accounts for the increased aggregation propensity. Furthermore, the computational modeling reveals a network of interactions with residue D76 as a keystone: this model allows predicting the stability of several point mutants. Overall, our study shows how the study of intrinsic dynamics in crystallo can provide crucial answers on protein stability and aggregation propensity. The comprehensive approach here presented may well be suited for the study of other folded amyloidogenic proteins.

PubMed: 29695721
DOI: 10.1038/s41467-018-04078-y

実験手法

X-RAY DIFFRACTION (2.1 Å)