6k9y
Crystal structure of human VAT-1
Structural highlights
FunctionVAT1_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 PubMedEukaryotic 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
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