Functional Diversification of the Chemical Landscapes of Yeast Sec14-like Phosphatidylinositol Transfer Protein Lipid-Binding Cavities

A1 Journal article (refereed)


Internal Authors/Editors


Publication Details

List of Authors: Ashutosh Tripathi, Elliott Martinez, Ahmad J Obaidullah, Marta G. Lete, Max Lönnfors, Danish Khan, Krishnakant G. Soni, Carl J Mousley, Glen E. Kellogg, Vytas A. Bankaitis
Publisher: American Society for Biochemistry and Molecular Biology, Inc.
Publication year: 2019
Journal: Journal of Biological Chemistry
Journal acronym: J Biol Chem
Volume number: 294
Issue number: 50
Start page: 19081
End page: 19098
ISSN: 1083-351X
eISSN: 1083-351X


Abstract

Phosphatidylinositol-transfer proteins (PITPs) are key regulators of lipid signaling in eukaryotic cells. These proteins both potentiate the activities of phosphatidylinositol (PtdIns) 4-OH kinases and help channel production of specific pools of phosphatidylinositol 4-phosphate (PtdIns(4)P) dedicated to specific biological outcomes. In this manner, PITPs represent a major contributor to the mechanisms by which the biological outcomes of phosphoinositide are diversified. The two-ligand priming model proposes that the engine by which Sec14-like PITPs potentiate PtdIns kinase activities is a heterotypic lipid-exchange cycle where PtdIns is a common exchange substrate among the Sec14-like PITP family, but the second exchange ligand varies with the PITP. A major prediction of this model is that second-exchangeable ligand identity will vary from PITP to PITP. To address the heterogeneity in the second exchange ligand for Sec14-like PITPs, we used structural, computational, and biochemical approaches to probe the diversities of the lipid-binding cavity microenvironments of the yeast Sec14-like PITPs. The collective data report that yeast Sec14-like PITP lipid-binding pockets indeed define diverse chemical microenvironments that translate into differential ligand-binding specificities across this protein family.

Last updated on 2020-26-05 at 03:19