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

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

Research output: Contribution to journalArticleScientificpeer-review

14 Citations (Scopus)


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.
Original languageUndefined/Unknown
Pages (from-to)19081–19098
JournalJournal of Biological Chemistry
Issue number50
Publication statusPublished - 2019
MoE publication typeA1 Journal article-refereed

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