8hql

Crystal structure of mouse SNX25 PX domain

spinqualitylabelsall models 8hql, resolution 2.40Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 8hql is a 5 chain structure with sequence from Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.4Å Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function SNX25_MOUSE May be involved in several stages of intracellular trafficking. Publication Abstract from PubMed 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 Galpha 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 Galpha(i/q) and their ability to bind GDP-bound (inactive form) Galpha(i/q). As a result, SNX25 recruits these RGS proteins to endosomes, leading to the termination of endosomal Galpha(i/q) signaling. Furthermore, we have found that the SNX25/RGS complex also exerts a negative regulatory effect on Galpha(i/q) signaling from the plasma membrane. This is achieved by recruiting Galpha(i/q) 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 Galpha(i/q) signaling, thereby uncovering a novel mechanism for terminating Galpha(i/q) signaling from endosomes. Importantly, this study expands our understanding of the regulation of GPCR-Galpha(i/q) signaling beyond the plasma membrane. Redox-modulated SNX25 as a novel regulator of GPCR-G protein signaling from endosomes.,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 Biol. 2024 Jun 22;75:103253. doi: 10.1016/j.redox.2024.103253. PMID:38936254 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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