VPS35

Vacuolar protein sorting-associated protein 35 is a is_associated_with::protein that in humans is encoded by the VPS35 is_associated_with::gene.

This gene belongs to a group of vacuolar protein sorting (VPS) genes. The encoded protein is a component of a large multimeric complex, termed the is_associated_with::retromer complex, involved in retrograde transport of proteins from is_associated_with::endosomes to the trans-Golgi network. The close structural similarity between the yeast and human proteins that make up this complex suggests a similarity in function. Expression studies in yeast and mammalian cells indicate that this protein interacts directly with VPS35, which serves as the core of the retromer complex.

Structure
Vps35 is the largest subunit of is_associated_with::retromer with the molecular weight of 92-kDa and functions as the central platform for the assembly of Vps26 and Vps29. Vps35 resembles many other helical solenoid proteins including AP adaptor protein complexes that are characterized with repeated structural units in a continuous superhelix arrangement involved in coated vesicle trafficking. The curved surface of the 6 even-numbered helices within solenoid structure with series of ridges separating is_associated_with::hydrophobic grooves function as potential cargo binding sites. The C-terminal of Vps35 contains an α-solenoid fold that fits into the metal binding pocket of Vps29.

A conserved PRLYL motif at the is_associated_with::N-terminus of Vps35 is involved in the binding of Vps26. The structural binding motifs enable this subunit to act as a linker between the SNX dimers and Vps trimer complex, and the binding sites targeting to the N-terminal region of SNX subunits are located at the both ends of the trimer. A study have shown that the knockdown of Vps35 in human is_associated_with::HEp-2 epithelial cells had defect on the is_associated_with::endosomal recycling of is_associated_with::transferrin by is_associated_with::DMT1 due to the mis-sorting of DMT1-II to the lysosomal membrane associated protein (is_associated_with::LAMP2) structures.