Molecular basis for sterol transport by StART-like lipid transfer domains.

Autor: Horenkamp FA; Department of Cell Biology, Yale University School of Medicine, New Haven, CT, USA., Valverde DP; Department of Cell Biology, Yale University School of Medicine, New Haven, CT, USA., Nunnari J; Department of Molecular and Cellular Biology, University of California, Davis, Davis, CA, USA., Reinisch KM; Department of Cell Biology, Yale University School of Medicine, New Haven, CT, USA karin.reinisch@yale.edu.
Jazyk: angličtina
Zdroj: The EMBO journal [EMBO J] 2018 Mar 15; Vol. 37 (6). Date of Electronic Publication: 2018 Feb 21.
DOI: 10.15252/embj.201798002
Abstrakt: Lipid transport proteins at membrane contact sites, where two organelles are closely apposed, play key roles in trafficking lipids between cellular compartments while distinct membrane compositions for each organelle are maintained. Understanding the mechanisms underlying non-vesicular lipid trafficking requires characterization of the lipid transporters residing at contact sites. Here, we show that the mammalian proteins in the lipid transfer proteins anchored at a membrane contact site (LAM) family, called GRAMD1a-c, transfer sterols with similar efficiency as the yeast orthologues, which have known roles in sterol transport. Moreover, we have determined the structure of a lipid transfer domain of the yeast LAM protein Ysp2p, both in its apo-bound and sterol-bound forms, at 2.0 Å resolution. It folds into a truncated version of the steroidogenic acute regulatory protein-related lipid transfer (StART) domain, resembling a lidded cup in overall shape. Ergosterol binds within the cup, with its 3-hydroxy group interacting with protein indirectly via a water network at the cup bottom. This ligand binding mode likely is conserved for the other LAM proteins and for StART domains transferring sterols.
(© 2018 The Authors.)
Databáze: MEDLINE
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