2MXC

Solution structure of the full length sorting nexin 3

Summary for 2MXC

• Entry DOI: 10.2210/pdb2mxc/pdb
• NMR Information: BMRB: 25402
• Descriptor: Sorting nexin-3 (1 entity in total)
• Functional Keywords: pi3p, snx3, membrane, endosome, protein transport
• Biological source: Homo sapiens (human)
• Cellular location: Early endosome : O60493
• Total number of polymer chains: 1
• Total formula weight: 19947.60

Authors

Lenoir, M.M.L.,Rajesh, S.S.R.,Gruenberg, J.J.G.,Overduin, M.M.O.,Kaur, J.J.K. (deposition date: 2014-12-20, release date: 2016-05-04, Last modification date: 2024-05-15)

Primary citation

Lenoir, M.,Ustunel, C.,Rajesh, S.,Kaur, J.,Moreau, D.,Gruenberg, J.,Overduin, M.
Phosphorylation of conserved phosphoinositide binding pocket regulates sorting nexin membrane targeting.
Nat Commun, 9:993-993, 2018

PubMed Abstract: Sorting nexins anchor trafficking machines to membranes by binding phospholipids. The paradigm of the superfamily is sorting nexin 3 (SNX3), which localizes to early endosomes by recognizing phosphatidylinositol 3-phosphate (PI3P) to initiate retromer-mediated segregation of cargoes to the trans-Golgi network (TGN). Here we report the solution structure of full length human SNX3, and show that PI3P recognition is accompanied by bilayer insertion of a proximal loop in its extended Phox homology (PX) domain. Phosphoinositide (PIP) binding is completely blocked by cancer-linked phosphorylation of a conserved serine beside the stereospecific PI3P pocket. This "PIP-stop" releases endosomal SNX3 to the cytosol, and reveals how protein kinases control membrane assemblies. It constitutes a widespread regulatory element found across the PX superfamily and throughout evolution including of fungi and plants. This illuminates the mechanism of a biological switch whereby structured PIP sites are phosphorylated to liberate protein machines from organelle surfaces.

PubMed: 29520003
DOI: 10.1038/s41467-018-03370-1

Experimental method

SOLUTION NMR