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

Forskningsoutput: TidskriftsbidragArtikelVetenskapligPeer review

8 Citeringar (Scopus)

Sammanfattning

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.
OriginalspråkOdefinierat/okänt
Sidor (från-till)19081–19098
TidskriftJournal of Biological Chemistry
Volym294
Utgåva50
DOI
StatusPublicerad - 2019
MoE-publikationstypA1 Tidskriftsartikel-refererad

Citera det här