title: The retromer subunit Vps26 has an arrestin fold and binds Vps35 through its C-terminal domain.
abstract: 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.
authors.affiliation: Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, US National Institutes of Health, US Department of Health and Human Services, Bethesda, Maryland 20892, USA.
authors.forename: Hang
authors.initials: H
authors.lastname: Shi
authors.forename: Raul
authors.initials: R
authors.lastname: Rojas
authors.forename: Juan S
authors.initials: JS
authors.lastname: Bonifacino
authors.forename: James H
authors.initials: JH
authors.lastname: Hurley
mesh_terms: D000595:Amino Acid Sequence; D019393:Arrestin / Q000737:chemistry*; D001665:Binding Sites; D018360:Crystallography, X-Ray; D006367:HeLa Cells; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D017386:Sequence Homology, Amino Acid; D033921:Vesicular Transport Proteins / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D019393:Arrestin; C498296:VPS26A protein, human; C419573:VPS35 protein, human; D033921:Vesicular Transport Proteins