J. Lipid Res.  Neurobiology of Lipids (ISSN1683-5506)
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Originally published In Press as doi:10.1194/jlr.M700460-JLR200 on December 15, 2007

Papers In Press, published online ahead of print March 1, 2008
J. Lipid Res., doi:10.1194/jlr.M700460-JLR200
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Journal of Lipid Research, Vol. 49, 644-653, March 2008
Copyright © 2008 by American Society for Biochemistry and Molecular Biology

Three-dimensional structure/function analysis of SCP-2-like2 reveals differences among SCP-2 family membersboxs

David H. Dyer*,{dagger}, Vilena Wessely{dagger}, Katrina T. Forest* and Que Lan1,{dagger}

* Department of Bacteriology, University of Wisconsin-Madison, Madison, WI 53706
{dagger} Department of Entomology, University of Wisconsin-Madison, Madison, WI 53706

boxs The online version of this article (available at http://www.jlr.org) contains supplementary data in the form of one table and one figure.

Published, JLR Papers in Press, December 15, 2007.

1 To whom correspondence should be addressed. e-mail: qlan{at}entomology.wisc.edu

Mosquito sterol carrier protein-2 (AeSCP-2) and sterol carrier protein-2-like2 (AeSCP-2L2) are members of the SCP-2 protein family with similar expression profiles in the mosquito life cycle. In an effort to understand how lipids can be transported by different SCP-2 proteins, the three-dimensional crystal structure of AeSCP-2L2 was solved at 1.7 Å resolution. AeSCP-2L2 forms a dimer and binds three fatty acids, one of which resides in a position within the internal cavity at a right angle to the others. This first report of ligand-bound dimerized protein in the SCP-2 protein family indicates that the family has a much more divergent mode of interaction with ligands than previously reported. The potential function of AeSCP-2L2 was investigated via in vivo incorporation of [3H]cholesterol and [3H]palmitic acid. Overexpression of AeSCP-2L2 in mosquito cells leads to an increased uptake of free fatty acid, whereas knockdown of AeSCP-2L2 in adult females decreases the accumulation of free fatty acid in the fat body from a blood meal. In contrast, overexpression or knockdown of AeSCP-2L2 has no effect on cholesterol uptake. Our results suggest that the main function of AeSCP-2L2 is as a general intracellular fatty acid carrier, as opposed to having a dedicated role in cholesterol transport.

Supplementary key words mosquito • cholesterol • fatty acid • sterol carrier protein-2







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