7VXV

Snapshots of Human PSMD10(Gankyrin) unfolding by urea: 0 hours incubation / Native

7VXV の概要

• エントリーDOI: 10.2210/pdb7vxv/pdb
• 分子名称: 26S proteasome non-ATPase regulatory subunit 10 (2 entities in total)
• 機能のキーワード: proteasomal chaperone, urea denaturation, oncoprotein
• 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: 24459.85

構造登録者

Mukund Sudharsan, M.G.,Dalvi, S.,Venkatraman, P. (登録日: 2021-11-13, 公開日: 2022-11-16, 最終更新日: 2023-11-29)

主引用文献

Medur Gurushankar, M.S.,Dalvi, S.,Venkatraman, P.
Snapshots of urea-induced early structural changes and unfolding of an ankyrin repeat protein at atomic resolution.
Protein Sci., 31:e4515-e4515, 2022

PubMed Abstract: Protein folding and unfolding is a complex process, underscored by the many proteotoxic diseases associated with misfolded proteins. Mapping pathways from a native structure to an unfolded protein or vice versa, identifying the intermediates, and defining the role of sequence and structure en route remain outstanding problems in the field. It is even more challenging to capture the events at atomistic resolution. X-ray diffraction has so far been used to understand how urea interacts with and unfolds two stable globular proteins. Here, we present the case study on PSMD10 , a prototype for a moderately stable, non-globular repeat protein, long and rigid, with its termini located at either end.   We define structural changes in the time dimension using low urea concentrations to arrive at the following conclusions. (a) Unfolding is rapidly initiated at the C-terminus, slowly at the N-terminus, and proceeds inwards from both ends. (b) C-terminus undergoes an α to 3 helix transition, representing the structure of a potential early unfolding intermediate before disorder sets in. (c) Distinct and progressive changes in the electrostatic landscape of PSMD10 were observed, indicative of conformational changes in the seemingly inflexible motif involved in protein-protein interaction. We believe this unique study will open up the field for better and bolder queries and increase the choice of model proteins for a better understanding of the challenging problems of protein folding, protein interactions, protein degradation, and diseases associated with misfolding.

PubMed: 36382986
DOI: 10.1002/pro.4515

実験手法

X-RAY DIFFRACTION (2.23 Å)