Structure and lipid transport mechanism of a StAR-related domain

Y Tsujishita, JH Hurley - Nature structural biology, 2000 - nature.com
Y Tsujishita, JH Hurley
Nature structural biology, 2000nature.com
The steroidogenic acute regulatory protein (StAR) regulates acute steroidogenesis in the
adrenal cortex and gonads by promoting the translocation of cholesterol to the mitochondrial
inner membrane where the first step in steriod biosynthesis is catalyzed. StAR-related lipid
transfer (START) domains occur in proteins involved in lipid transport and metabolism,
signal transduction, and transcriptional regulation. The 2.2 Å resolution crystal structure of
the START domain of human MLN64 reported here reveals an α/β fold built around a U …
Abstract
The steroidogenic acute regulatory protein (StAR) regulates acute steroidogenesis in the adrenal cortex and gonads by promoting the translocation of cholesterol to the mitochondrial inner membrane where the first step in steriod biosynthesis is catalyzed. StAR-related lipid transfer (START) domains occur in proteins involved in lipid transport and metabolism, signal transduction, and transcriptional regulation. The 2.2 Å resolution crystal structure of the START domain of human MLN64 reported here reveals an α/β fold built around a U-shaped incomplete β-barrel. The interior of the protein encompasses a 26× 12× 11 Å hydrophobic tunnel that is large enough to bind a single cholesterol molecule. The StAR and MLN64 START domains bind 1 mole of 14 C cholesterol per mole of protein in vitro. Based on the START domain structure and cholesterol binding stoichiometry, it is proposed that StAR acts by shuttling cholesterol molecules one at a time through the intermembrane space of the mitochondrion.
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