8HQL

Crystal structure of mouse SNX25 PX domain

Summary for 8HQL

• Entry DOI: 10.2210/pdb8hql/pdb
• Descriptor: Sorting nexin-25, PENTAETHYLENE GLYCOL, GLYCEROL, ... (6 entities in total)
• Functional Keywords: px domain, sorting nexins, snx25, protein transport
• Biological source: Mus musculus (house mouse)
• Total number of polymer chains: 5
• Total formula weight: 79857.00

Authors

Yu, Z.,Xu, J.,Liu, J. (deposition date: 2022-12-13, release date: 2023-12-20, Last modification date: 2024-10-23)

Primary citation

Zhang, Y.,Yu, Z.,Sun, M.,Du, R.,Gao, H.,Dai, Q.,Dong, Y.,Liu, C.,Yin, M.,Xu, T.,Zhang, X.,Liu, J.,Xu, J.
Redox-modulated SNX25 as a novel regulator of GPCR-G protein signaling from endosomes.
Redox Biol, 75:103253-103253, 2024

PubMed Abstract: GPCR-G protein signaling from endosomes plays a crucial role in various physiological and pathological processes. However, the mechanism by which endosomal G protein signaling is terminated remains largely unknown. In this study, we aimed to investigate the regulatory mechanisms involved in terminating the signaling of Gα subunits from endosomes. Through structural analysis and cell-based assays, we have discovered that SNX25, a protein that targets endosomes via its PXA or PXC domain, interacts with regulator of G protein signaling (RGS) proteins (including RGS2, RGS4, RGS8, and RGS17) in a redox-regulated manner. The interaction between SNX25 and these RGS proteins enhances their GTPase-accelerating activity towards Gα and their ability to bind GDP-bound (inactive form) Gα. As a result, SNX25 recruits these RGS proteins to endosomes, leading to the termination of endosomal Gα signaling. Furthermore, we have found that the SNX25/RGS complex also exerts a negative regulatory effect on Gα signaling from the plasma membrane. This is achieved by recruiting Gα to endosomes and preventing its activation on the plasma membrane. Our findings shed light on the previously unknown role of redox-modulated SNX25 in inhibiting Gα signaling, thereby uncovering a novel mechanism for terminating Gα signaling from endosomes. Importantly, this study expands our understanding of the regulation of GPCR-Gα signaling beyond the plasma membrane.

PubMed: 38936254
DOI: 10.1016/j.redox.2024.103253

Experimental method

X-RAY DIFFRACTION (2.4 Å)