7VXW

Snapshots of Human PSMD10(Gankyrin) unfolding by urea: 1 hour incubation

Summary for 7VXW

• Entry DOI: 10.2210/pdb7vxw/pdb
• Related: 7VXV
• Descriptor: 26S proteasome non-ATPase regulatory subunit 10, UREA (3 entities in total)
• Functional Keywords: proteasomal chaperone, urea denaturation, oncoprotein
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 1
• Total formula weight: 24640.02

Authors

Mukund Sudharsan, M.G.,Dalvi, S.,Venkatraman, P. (deposition date: 2021-11-13, release date: 2022-11-16, Last modification date: 2023-11-29)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.22 Å)