4GXB

Structure of the SNX17 atypical FERM domain bound to the NPxY motif of P-selectin

Summary for 4GXB

• Entry DOI: 10.2210/pdb4gxb/pdb
• Related: 1HES 3FOG 3LUI
• Descriptor: Sorting nexin-17, P-selectin, GLYCEROL, ... (4 entities in total)
• Functional Keywords: ferm domain, protein transport-cell adhesion complex, protein transport/cell adhesion
• Biological source: Homo sapiens (human); More
• Cellular location: Cytoplasm: Q15036; Membrane; Single-pass type I membrane protein: Q01102
• Total number of polymer chains: 2
• Total formula weight: 36366.47

Authors

Ghai, R.,Bugarcic, A.,Liu, H.,Norwood, S.J.,Li, S.S.,Teasdale, R.D.,Collins, B.M. (deposition date: 2012-09-04, release date: 2013-03-13, Last modification date: 2024-03-20)

Primary citation

Ghai, R.,Bugarcic, A.,Liu, H.,Norwood, S.J.,Skeldal, S.,Coulson, E.J.,Li, S.S.,Teasdale, R.D.,Collins, B.M.
Structural basis for endosomal trafficking of diverse transmembrane cargos by PX-FERM proteins.
Proc.Natl.Acad.Sci.USA, 110:E643-E652, 2013

PubMed Abstract: Transit of proteins through the endosomal organelle following endocytosis is critical for regulating the homeostasis of cell-surface proteins and controlling signal transduction pathways. However, the mechanisms that control these membrane-transport processes are poorly understood. The Phox-homology (PX) domain-containing proteins sorting nexin (SNX) 17, SNX27, and SNX31 have emerged recently as key regulators of endosomal recycling and bind conserved Asn-Pro-Xaa-Tyr-sorting signals in transmembrane cargos via an atypical band, 4.1/ezrin/radixin/moesin (FERM) domain. Here we present the crystal structure of the SNX17 FERM domain bound to the sorting motif of the P-selectin adhesion protein, revealing both the architecture of the atypical FERM domain and the molecular basis for recognition of these essential sorting sequences. We further show that the PX-FERM proteins share a promiscuous ability to bind a wide array of putative cargo molecules, including receptor tyrosine kinases, and propose a model for their coordinated molecular interactions with membrane, cargo, and regulatory proteins.

PubMed: 23382219
DOI: 10.1073/pnas.1216229110

Experimental method

X-RAY DIFFRACTION (1.8 Å)