7WZC

An open conformation Form2 of switch II for RhoA GDP-bound state

7WZC の概要

• エントリーDOI: 10.2210/pdb7wzc/pdb
• 分子名称: Transforming protein RhoA, GLYCEROL, GUANOSINE-5'-DIPHOSPHATE, ... (5 entities in total)
• 機能のキーワード: small gtpase, rho family member, cell invasion
• 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: 21496.46

構造登録者

Jiang, H.,Luo, C. (登録日: 2022-02-17, 公開日: 2023-02-22, 最終更新日: 2023-11-29)

主引用文献

Jiang, H.,Zu, S.,Lu, Y.,Sun, Z.,Adeerjiang, A.,Guo, Q.,Zhang, H.,Dong, C.,Wu, Q.,Ding, H.,Du, D.,Wang, M.,Liu, C.,Tang, Y.,Liang, Z.,Luo, C.
A RhoA structure with switch II flipped outward revealed the conformational dynamics of switch II region.
J.Struct.Biol., 215:107942-107942, 2023

PubMed Abstract: Small GTPase RhoA switches from GTP-bound state to GDP-bound state by hydrolyzing GTP, which is accelerated by GTPases activating proteins (GAPs). However, less study of RhoA structural dynamic changes was conducted during this process, which is essential for understanding the molecular mechanism of GAP dissociation. Here, we solved a RhoA structure in GDP-bound state with switch II flipped outward. Because lacking the intermolecular interactions with guanine nucleotide, we proposed this conformation of RhoA could be an intermediate after GAP dissociation. Further molecular dynamics simulations found the conformational changes of switch regions are indeed existing in RhoA and involved in the regulation of GAP dissociation and GEF recognition. Besides, the guanine nucleotide binding pocket extended to switch II region, indicating a potential "druggable" cavity for RhoA. Taken together, our study provides a deeper understanding of the dynamic properties of RhoA switch regions and highlights the direction for future drug development.

PubMed: 36781028
DOI: 10.1016/j.jsb.2023.107942

実験手法

X-RAY DIFFRACTION (1.7994492129 Å)