5CFH

human beta-2 microglobulin double mutant W60G-Y63W

5CFH の概要

• エントリーDOI: 10.2210/pdb5cfh/pdb
• 分子名称: Beta-2-microglobulin (2 entities in total)
• 機能のキーワード: aggregation propensity, amyloid, beta-sandwitch, fold stability, 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: 11773.23

構造登録者

Sala, B.M.,De Rosa, M.,Bolognesi, M.,Ricagno, S. (登録日: 2015-07-08, 公開日: 2016-05-18, 最終更新日: 2024-11-13)

主引用文献

Camilloni, C.,Sala, B.M.,Sormanni, P.,Porcari, R.,Corazza, A.,De Rosa, M.,Zanini, S.,Barbiroli, A.,Esposito, G.,Bolognesi, M.,Bellotti, V.,Vendruscolo, M.,Ricagno, S.
Rational design of mutations that change the aggregation rate of a protein while maintaining its native structure and stability.
Sci Rep, 6:25559-25559, 2016

PubMed Abstract: A wide range of human diseases is associated with mutations that, destabilizing proteins native state, promote their aggregation. However, the mechanisms leading from folded to aggregated states are still incompletely understood. To investigate these mechanisms, we used a combination of NMR spectroscopy and molecular dynamics simulations to compare the native state dynamics of Beta-2 microglobulin (β2m), whose aggregation is associated with dialysis-related amyloidosis, and its aggregation-resistant mutant W60G. Our results indicate that W60G low aggregation propensity can be explained, beyond its higher stability, by an increased average protection of the aggregation-prone residues at its surface. To validate these findings, we designed β2m variants that alter the aggregation-prone exposed surface of wild-type and W60G β2m modifying their aggregation propensity. These results allowed us to pinpoint the role of dynamics in β2m aggregation and to provide a new strategy to tune protein aggregation by modulating the exposure of aggregation-prone residues.

PubMed: 27150430
DOI: 10.1038/srep25559

実験手法

X-RAY DIFFRACTION (1.49 Å)