PDBsum entry 4p2i

Signaling protein

PDB id: 4p2i

Contents

Protein chains

117 a.a.

Waters ×309

PDB id:

4p2i

Name:

Signaling protein

Title:

Crystal structure of the mouse snx19 px domain

Structure:

Mkiaa0254 protein. Chain: a, b. Engineered: yes

Source:

Mus musculus. Mouse. Organism_taxid: 10090. Gene: snx19, mkiaa0254. Expressed in: escherichia coli. Expression_system_taxid: 562

Resolution:

1.90Å R-factor: 0.213 R-free: 0.247

Authors:

B.M.Collins

Key ref:

C.Mas et al. (2014). Structural basis for different phosphoinositide specificities of the PX domains of sorting nexins regulating G-protein signaling. J Biol Chem, 289, 28554-28568. PubMed id: 25148684 DOI: 10.1074/jbc.M114.595959

Date:

04-Mar-14 Release date: 03-Sep-14

Protein chains

Q6P4T1  (SNX19_MOUSE) -  Sorting nexin-19 from Mus musculus

Seq: 997 a.a.

Struc: 117 a.a.

DOI no: 10.1074/jbc.M114.595959

J Biol Chem 289:28554-28568 (2014)

PubMed id: 25148684

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

C.Mas, S.J.Norwood, A.Bugarcic, G.Kinna, N.Leneva, O.Kovtun, R.Ghai, L.E.Ona Yanez, J.L.Davis, R.D.Teasdale, B.M.Collins.

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.