Structural basis of sterol binding and transport by a yeast StARkin domain

The Journal of Biological Chemistry
Julian-Alexander JentschAnant K Menon

Abstract

The StARkin superfamily comprises proteins with steroidogenic acute regulatory protein-related lipid transfer (StART) domains that are implicated in intracellular, non-vesicular lipid transport. A new family of membrane-anchored StARkins was recently identified, including six members, Lam1-Lam6, in the yeast Saccharomyces cerevisiae. Lam1-Lam4 are anchored to the endoplasmic reticulum (ER) membrane at sites where the ER is tethered to the plasma membrane and proposed to be involved in sterol homeostasis in yeast. To better understand the biological roles of these proteins, we carried out a structure-function analysis of the second StARkin domain of Lam4, here termed Lam4S2. NMR experiments indicated that Lam4S2 undergoes specific conformational changes upon binding sterol, and fluorescence-based assays revealed that it catalyzes sterol transport between vesicle populations in vitro, exhibiting a preference for vesicles containing anionic lipids. Using such vesicles, we found that sterols are transported at a rate of ∼50 molecules per Lam4S2 per minute. Crystal structures of Lam4S2, with and without bound sterol, revealed a largely hydrophobic but surprisingly accessible sterol-binding pocket with the 3-OH group of the sterol or...Continue Reading

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Citations

Dec 5, 2019·ELife·George KhelashviliAnant K Menon
Apr 23, 2020·The Journal of Cell Biology·Magdalena MarekSophie G Martin
Mar 10, 2019·Nature Communications·Xeni MiliaraThomas Langer
Aug 15, 2020·Frontiers in Cell and Developmental Biology·Mohammad F ZamanChristopher T Beh
Jun 20, 2019·Biochemistry. Biokhimii︠a︡·K V Tugaeva, N N Sluchanko
Mar 9, 2021·Frontiers in Cell and Developmental Biology·Bailey HewlettThierry Galli
Apr 4, 2021·International Journal of Molecular Sciences·Samantha Katarzyna Dziurdzik, Elizabeth Conibear
May 2, 2021·Biochimica Et Biophysica Acta. Molecular and Cell Biology of Lipids·Tomoki Naito, Yasunori Saheki
Apr 3, 2020·Journal of Chemical Information and Modeling·Laust MoesgaardJacob Kongsted

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