NDLI: Cholesterol Binding Does Not Predict Activity of the Steroidogenic Acute Regulatory Protein, StAR

Content Provider	Journal of Biological Chemistry (JBC)
Author	Baker, Bo Y. Epand, Raquel F. Epand, Richard M. Miller, Walter L.
Abstract	Steroidogenic acute regulatory protein (StAR) stimulates adrenal and gonadal steroidogenesis by increasing the influx of cholesterol into mitochondria, where it is converted to pregnenolone to initiate steroidogenesis. StAR acts on the outer mitochondrial membrane where each molecule stimulates the mitochondrial import of several hundred molecules of cholesterol, but the precise mechanism of the action of StAR remains uncertain. StAR has a sterol-binding pocket that can accommodate one molecule of cholesterol. Direct assays show that StAR can bind cholesterol with stoichiometry approaching 1:1, and several disease-causing mutants with decreased or absent activity have correspondingly decreased cholesterol binding. We show that the StAR mutant R182L, which causes severe disease and is devoid of measurable activity in transfected cells or with isolated steroidogenic mitochondria, nevertheless, can bind as much [14C]- or NBD-cholesterol as wild-type StAR under equilibrium conditions and can transfer cholesterol between liposomes in vitro. Similarly, the artificial mutant S195A had 46.5% of the activity of wild-type StAR but bound cholesterol indistinguishably from wild-type. Competition assays showed that the rate of binding (t½on) for R182L was only 36% of the wild-type and the rate of dissociation (t½off) was 57% of wild-type, whereas the t½on and t½off for S195A and S195D were essentially the same for wild-type. These data indicate that cholesterol binding and transfer activities are distinct from its activity to induce steroidogenesis. StAR appears to act by other mechanisms in addition to cholesterol binding.
Related Links	http://www.jbc.org/content/282/14/10223.abstract
Ending Page	10232
Starting Page	10223
Page Count	10
File Format	HTM / HTML PDF
ISSN	00219258
Journal	Journal of Biological Chemistry (JBC)
Issue Number	14
Volume Number	282
DOI	10.1074/jbc.M611221200
e-ISSN	1083351X
Language	English
Publisher	American Society for Biochemistry and Molecular Biology
Publisher Date	2007-04-06
Access Restriction	Open
Subject Keyword	Membrane Transport, Structure, Function, and Biogenesis
Content Type	Text
Resource Type	Article
Subject	Cell Biology Biochemistry Molecular Biology

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