Structural basis for different phosphoinositide specificities of the PX domains of sorting nexins regulating G-protein signaling

Mas, Caroline, Norwood, Suzanne J., Bugarcic, Andrea, Kinna, Genevieve, Leneva, Natalya, Kovtun, Oleksiy, Ghai, Rajesh, Yanez, Lorena E. Ona, Davis, Jasmine L., Teasdale, Rohan D. and Collins, Brett M. (2014) Structural basis for different phosphoinositide specificities of the PX domains of sorting nexins regulating G-protein signaling. Journal of Biological Chemistry, 289 41: 28554-28568. doi:10.1074/jbc.M114.595959

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Author Mas, Caroline
Norwood, Suzanne J.
Bugarcic, Andrea
Kinna, Genevieve
Leneva, Natalya
Kovtun, Oleksiy
Ghai, Rajesh
Yanez, Lorena E. Ona
Davis, Jasmine L.
Teasdale, Rohan D.
Collins, Brett M.
Title Structural basis for different phosphoinositide specificities of the PX domains of sorting nexins regulating G-protein signaling
Journal name Journal of Biological Chemistry   Check publisher's open access policy
ISSN 1083-351X
2152-2561
Publication date 2014-10-10
Year available 2014
Sub-type Article (original research)
DOI 10.1074/jbc.M114.595959
Open Access Status File (Publisher version)
Volume 289
Issue 41
Start page 28554
End page 28568
Total pages 15
Place of publication New York, NY, United States
Publisher Academic Journals
Collection year 2015
Language eng
Abstract Sorting nexins (SNXs) or phox homology (PX) domain containing proteins are central regulators of cell trafficking and signaling. A subfamily of PX domain proteins possesses two unique PX-associated domains, as well as a regulator of G protein-coupled receptor signaling (RGS) domain that attenuates Gαs-coupled G protein-coupled receptor signaling. Here we delineate the structural organization of these RGS-PX proteins, revealing a protein family with a modular architecture that is conserved in all eukaryotes. The one exception to this is mammalian SNX19, which lacks the typical RGS structure but preserves all other domains. The PX domain is a sensor of membrane phosphoinositide lipids and we find that specific sequence alterations in the PX domains of the mammalian RGS-PX proteins, SNX13, SNX14, SNX19, and SNX25, confer differential phosphoinositide binding preferences. Although SNX13 and SNX19 PX domains bind the early endosomal lipid phosphatidylinositol 3-phosphate, SNX14 shows no membrane binding at all. Crystal structures of the SNX19 and SNX14 PX domains reveal key differences, with alterations in SNX14 leading to closure of the binding pocket to prevent phosphoinositide association. Our findings suggest a role for alternative membrane interactions in spatial control of RGS-PX proteins in cell signaling and trafficking.
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2015 Collection
Institute for Molecular Bioscience - Publications
 
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