Vacuolar protein sorting-associated protein 35 is a protein that in humans is encoded by the VPS35gene.[1][2]
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 retromer complex, involved in retrograde transport of proteins from 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.[2]
Structure
Vps35 is the largest subunit of retromer with the molecular weight of 92-kDa and functions as the central platform for the assembly of Vps26 and Vps29.[3] 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 hydrophobic grooves function as potential cargo binding sites.[4] The C-terminal of Vps35 contains an α-solenoid fold that fits into the metal binding pocket of Vps29.[5]
A conserved PRLYL motif at the N-terminus of Vps35 is involved in the binding of Vps26.[6][7] 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 has shown that the knockdown of Vps35 in human HEp-2 epithelial cells had defect on the endosomal recycling of transferrin by DMT1 due to the mis-sorting of DMT1-II to the lysosomal membrane associated protein (LAMP2) structures.[8]
References
↑Zhang P, Yu L, Gao J, Fu Q, Dai F, Zhao Y, Zheng L, Zhao S (Jan 2001). "Cloning and characterization of human VPS35 and mouse Vps35 and mapping of VPS35 to human chromosome 16q13-q21". Genomics. 70 (2): 253–7. doi:10.1006/geno.2000.6380. PMID11112353.
↑Collins BM, Skinner CF, Watson PJ, Seaman MN, Owen DJ (July 2005). "Vps29 has a phosphoesterase fold that acts as a protein interaction scaffold for retromer assembly". Nat. Struct. Mol. Biol. 12 (7): 594–602. doi:10.1038/nsmb954. PMID15965486.
↑Tabuchi M, Yanatori I, Kawai Y, Kishi F (March 2010). "Retromer-mediated direct sorting is required for proper endosomal recycling of the mammalian iron transporter DMT1". J. Cell Sci. 123 (Pt 5): 756–66. doi:10.1242/jcs.060574. PMID20164305.
Further reading
Maruyama K, Sugano S (1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene. 138 (1–2): 171–4. doi:10.1016/0378-1119(94)90802-8. PMID8125298.
Andersson B, Wentland MA, Ricafrente JY, Liu W, Gibbs RA (1996). "A "double adaptor" method for improved shotgun library construction". Anal. Biochem. 236 (1): 107–13. doi:10.1006/abio.1996.0138. PMID8619474.
Bonaldo MF, Lennon G, Soares MB (1997). "Normalization and subtraction: two approaches to facilitate gene discovery". Genome Res. 6 (9): 791–806. doi:10.1101/gr.6.9.791. PMID8889548.
Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S (1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene. 200 (1–2): 149–56. doi:10.1016/S0378-1119(97)00411-3. PMID9373149.
Edgar AJ, Polak JM (2000). "Human homologues of yeast vacuolar protein sorting 29 and 35". Biochem. Biophys. Res. Commun. 277 (3): 622–30. doi:10.1006/bbrc.2000.3727. PMID11062004.
