Three-dimensional structure/function analysis of SCP-2-like2 reveals differences among SCP-2 family members.
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 A 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 [(3)H]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.
Dyer
David H
DH
Department of Bacteriology, University of Wisconsin-Madison, Madison, WI 53706, USA.
Wessely
Vilena
V
Forest
Katrina T
KT
Lan
Que
Q
D000818:Animals; D001692:Biological Transport; D002352:Carrier Proteins / Q000737:chemistry*; D018360:Crystallography, X-Ray; D009033:Culicidae; D005227:Fatty Acids / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D019476:Insect Proteins / Q000737:chemistry*; D050356:Lipid Metabolism; D011487:Protein Conformation; D014316:Tritium
D002352:Carrier Proteins; D005227:Fatty Acids; D019476:Insect Proteins; C072087:sterol carrier proteins; D014316:Tritium