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Structural basis for interorganelle phospholipid transport mediated by VAT-1.

ABSTRACT: 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 Å 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 subdomains, 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 protruded from the molecule and facilitated binding to the acidic-lipid membranes, thereby achieving efficient phospholipid transfer.

SUBMITTER: Watanabe Y

PROVIDER: S-EPMC7062155 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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Structural basis for interorganelle phospholipid transport mediated by VAT-1.

Watanabe Yasunori Y Tamura Yasushi Y Kakuta Chika C Watanabe Seiya S Endo Toshiya T

The Journal of biological chemistry 20200131 10

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 Å resolution. We found that VAT-1 transferred not only phosphatidylserine but also other acidic phospholipids between membranes <i>in vitro</i> Structure-based mutational analyses showed the presence of a possible lipid-binding cav ...[more]

PMID: 32005660

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