Submitted on October 11, 2007
Revised on December 14, 2007
Accepted on December 14, 2007
3-D structure/function analysis of sterol carrier protein-2-like2 reveals differences among SCP-2 family members
David H. Dyer, Vilena Wessely, Katrina T. Forest, and Que Lan
Entomology, University of Wisconsin-Madison, Madison, WI 53706
Corresponding Author: 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 3-dimensional crystal structure of AeSCP-2L2 was solved at 1.7 Å resolution. AeSCP-2L2 forms a dimer and binds 3 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 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. Over-expression of AeSCP-2L2 in mosquito cells leads to increased uptake of free fatty acid, whereas knockdown of AeSCP-2L2 in adult females decreases accumulation of free fatty acid in the fat body from a blood meal. In contrast, over-expression 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 a dedicated role in cholesterol transport.
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