The retromer subunit Vps26 has an arrestin fold and binds Vps35 through its C-terminal domain

Nat Struct Mol Biol. 2006 Jun;13(6):540-8. doi: 10.1038/nsmb1103. Epub 2006 May 28.


The mammalian retromer complex consists of SNX1, SNX2, Vps26, Vps29 and Vps35, and retrieves lysosomal enzyme receptors from endosomes to the trans-Golgi network. The structure of human Vps26A at 2.1-A resolution reveals two curved beta-sandwich domains connected by a polar core and a flexible linker. Vps26 has an unpredicted structural relationship to arrestins. The Vps35-binding site on Vps26 maps to a mobile loop spanning residues 235-246, near the tip of the C-terminal domain. The loop is phylogenetically conserved and provides a mechanism for Vps26 integration into the complex that leaves the rest of the structure free for engagements with membranes and for conformational changes. Hydrophobic residues and a glycine in this loop are required for integration into the retromer complex and endosomal localization of human Vps26, and for the function of yeast Vps26 in carboxypeptidase Y sorting.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Arrestin / chemistry*
  • Binding Sites
  • Crystallography, X-Ray
  • HeLa Cells
  • Humans
  • Models, Molecular
  • Molecular Sequence Data
  • Protein Conformation
  • Sequence Homology, Amino Acid
  • Vesicular Transport Proteins / chemistry*
  • Vesicular Transport Proteins / metabolism*


  • Arrestin
  • VPS26A protein, human
  • VPS35 protein, human
  • Vesicular Transport Proteins

Associated data

  • PDB/2FAU