Structural basis for endosomal trafficking of diverse transmembrane cargos by PX-FERM proteins

Proc Natl Acad Sci U S A. 2013 Feb 19;110(8):E643-52. doi: 10.1073/pnas.1216229110. Epub 2013 Feb 4.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Binding Sites
  • Endosomes / metabolism*
  • Models, Molecular
  • Molecular Sequence Data
  • Protein Conformation
  • Protein Transport
  • Sorting Nexins / chemistry
  • Sorting Nexins / metabolism*


  • Sorting Nexins

Associated data

  • PDB/4GXB