The retromer subunit Vps26 has an arrestin fold and binds Vps35 through its C-terminal domain.
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.
Shi
Hang
H
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.
Rojas
Raul
R
Bonifacino
Juan S
JS
Hurley
James H
JH
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*
D019393:Arrestin; C498296:VPS26A protein, human; C419573:VPS35 protein, human; D033921:Vesicular Transport Proteins