Structural highlights
Function
VAT1_HUMAN Possesses ATPase activity (By similarity). Plays a part in calcium-regulated keratinocyte activation in epidermal repair mechanisms. Has no effect on cell proliferation. Negatively regulates mitochondrial fusion in cooperation with mitofusin proteins (MFN1-2).[1] [2] [3]
Publication Abstract from PubMed
Eukaryotic cells are compartmentalized to form organelles, whose functions rely on proper phospholipid and protein transport. Here we determined the crystal structure of human VAT-1, a cytosolic soluble protein that was suggested to transfer phosphatidylserine, at 2.2 A resolution. We found that VAT-1 transferred not only phosphatidylserine but also other acidic phospholipids between membranes in vitro. Structure-based mutational analyses showed the presence of a possible lipid-binding cavity at the interface between the two sub-domains, and two tyrosine residues in the flexible loops facilitated phospholipid transfer, likely by functioning as a gate to this lipid-binding cavity. We also found that a basic and hydrophobic loop with two tryptophan residues was protruded from the molecule and facilitated binding to the acidic-lipid membranes, thereby achieving efficient phospholipid transfer.
Structural basis for inter-organelle phospholipid transport mediated by VAT-1.,Watanabe Y, Tamura Y, Kakuta C, Watanabe S, Endo T J Biol Chem. 2020 Jan 31. pii: RA119.011019. doi: 10.1074/jbc.RA119.011019. PMID:32005660[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Koch J, Foekens J, Timmermans M, Fink W, Wirzbach A, Kramer MD, Schaefer BM. Human VAT-1: a calcium-regulated activation marker of human epithelial cells. Arch Dermatol Res. 2003 Sep;295(5):203-10. doi: 10.1007/s00403-003-0421-8. Epub, 2003 Jul 30. PMID:12898150 doi:http://dx.doi.org/10.1007/s00403-003-0421-8
- ↑ Eura Y, Ishihara N, Oka T, Mihara K. Identification of a novel protein that regulates mitochondrial fusion by modulating mitofusin (Mfn) protein function. J Cell Sci. 2006 Dec 1;119(Pt 23):4913-25. doi: 10.1242/jcs.03253. Epub 2006 Nov , 14. PMID:17105775 doi:http://dx.doi.org/10.1242/jcs.03253
- ↑ Mertsch S, Becker M, Lichota A, Paulus W, Senner V. Vesicle amine transport protein-1 (VAT-1) is upregulated in glioblastomas and promotes migration. Neuropathol Appl Neurobiol. 2009 Aug;35(4):342-52. doi:, 10.1111/j.1365-2990.2009.00993.x. PMID:19508442 doi:http://dx.doi.org/10.1111/j.1365-2990.2009.00993.x
- ↑ Watanabe Y, Tamura Y, Kakuta C, Watanabe S, Endo T. Structural basis for inter-organelle phospholipid transport mediated by VAT-1. J Biol Chem. 2020 Jan 31. pii: RA119.011019. doi: 10.1074/jbc.RA119.011019. PMID:32005660 doi:http://dx.doi.org/10.1074/jbc.RA119.011019
