7wf9

Publication Abstract from PubMed

As a subgroup of sorting nexins (SNXs) that contain regulator of G protein signaling homology (RH) domain, SNX-RH proteins, including SNX13, SNX14 and SNX25, were proposed to play bifunctional roles in protein sorting and GPCR signaling regulation. However, mechanistic details of SNX-RH proteins functioning via RH domain remain to be illustrated. Here, we delineate crystal structures of the RH domains of SNX13 and SNX25, revealing a homodimer of SNX13 RH domain mediated by unique extended alpha4 and alpha5 helices, and a thiol modulated homodimer of SNX25-RH triggered by a unique cysteine on alpha6 helix. Further studies showed that RH domains of SNX-RH do not possess binding capacity toward Galpha subunits, owing to the lack of critical residues for interaction. Thus, this study identifies a group of novel non-canonical RH domains that can act as a dimerization module in sorting nexins, which provides structural basis for mechanism studies on SNX-RH protein functions.

Structural Studies Reveal Unique Non-canonical Regulators of G Protein Signaling Homology (RH) Domains in Sorting Nexins.,Zhang Y, Chen R, Dong Y, Zhu J, Su K, Liu J, Xu J J Mol Biol. 2022 Sep 11;434(21):167823. doi: 10.1016/j.jmb.2022.167823. PMID:36103920^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.