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

J Lipid Res. 2008 Mar;49(3):644-53. doi: 10.1194/jlr.M700460-JLR200. Epub 2007 Dec 15.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Biological Transport
  • Carrier Proteins / chemistry*
  • Crystallography, X-Ray
  • Culicidae
  • Fatty Acids / metabolism
  • Female
  • Gene Expression
  • Insect Proteins / chemistry*
  • Lipid Metabolism
  • Protein Conformation
  • Tritium


  • Carrier Proteins
  • Fatty Acids
  • Insect Proteins
  • sterol carrier proteins
  • Tritium