3bdq Citations

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

J Lipid Res 49 644-53 (2008)
Cited: 18 times
EuropePMC logo PMID: 18084051

Abstract

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.

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Reviews citing this publication (2)

  1. A novel model of cholesterol efflux from lipid-loaded cells. Luo DX, Cao DL, Xiong Y, Peng XH, Liao DF. Acta Pharmacol. Sin. 31 1243-1257 (2010)
  2. A history of studies that examine the interactions of Toxoplasma with its host cell: Emphasis on in vitro models. Boyle JP, Radke JR. Int. J. Parasitol. 39 903-914 (2009)

Articles citing this publication (14)

  1. The biological activity of alpha-mangostin, a larvicidal botanic mosquito sterol carrier protein-2 inhibitor. Larson RT, Lorch JM, Pridgeon JW, Becnel JJ, Clark GG, Lan Q. J. Med. Entomol. 47 249-257 (2010)
  2. In vivo functional genomic studies of sterol carrier protein-2 gene in the yellow fever mosquito. Peng R, Maklokova VI, Chandrashekhar JH, Lan Q. PLoS ONE 6 e18030 (2011)
  3. Effects of mutations in Aedes aegypti sterol carrier protein-2 on the biological function of the protein. Radek JT, Dyer DH, Lan Q. Biochemistry 49 7532-7541 (2010)
  4. A new structural form in the SAM/metal-dependent o‑methyltransferase family: MycE from the mycinamicin biosynthetic pathway. Akey DL, Li S, Konwerski JR, Confer LA, Bernard SM, Anzai Y, Kato F, Sherman DH, Smith JL. J. Mol. Biol. 413 438-450 (2011)
  5. Sterol Carrier Protein 2, a Critical Host Factor for Dengue Virus Infection, Alters the Cholesterol Distribution in Mosquito Aag2 Cells. Fu Q, Inankur B, Yin J, Striker R, Lan Q. J. Med. Entomol. 52 1124-1134 (2015)
  6. NMR and X-ray structures of the putative sterol carrier protein 2 from Thermus thermophilus HB8 show conformational changes. Goroncy AK, Murayama K, Shirouzu M, Kuramitsu S, Kigawa T, Yokoyama S. J. Struct. Funct. Genomics 11 247-256 (2010)
  7. THAP and ATF-2 regulated sterol carrier protein-2 promoter activities in the larval midgut of the yellow fever mosquito, Aedes aegypti. Peng R, Fu Q, Hong H, Schwaegler T, Lan Q. PLoS ONE 7 e46948 (2012)
  8. The crystal structure of sterol carrier protein 2 from Yarrowia lipolytica and the evolutionary conservation of a large, non-specific lipid-binding cavity. De Berti FP, Capaldi S, Ferreyra R, Burgardt N, Acierno JP, Klinke S, Monaco HL, Ermácora MR. J. Struct. Funct. Genomics 14 145-153 (2013)
  9. Mosquitocidal properties of natural product compounds isolated from Chinese herbs and synthetic analogs of curcumin. Anstrom DM, Zhou X, Kalk CN, Song B, Lan Q. J. Med. Entomol. 49 350-355 (2012)
  10. Structural and functional analyses of a sterol carrier protein in Spodoptera litura. Zhang L, Li D, Xu R, Zheng S, He H, Wan J, Feng Q. PLoS ONE 9 e81542 (2014)
  11. Yellow fever mosquito sterol carrier protein-2 gene structure and transcriptional regulation. Vyazunova I, Lan Q. Insect Mol. Biol. 19 205-215 (2010)
  12. Characterization of the oxysterol-binding protein gene family in the yellow fever mosquito, Aedes aegypti. Fu Q, Lynn-Miller A, Lan Q. Insect Mol. Biol. 20 541-552 (2011)
  13. Structural basis of cholesterol binding by a novel clade of dendritic cell modulators from ticks. Roversi P, Johnson S, Preston SG, Nunn MA, Paesen GC, Austyn JM, Nuttall PA, Lea SM. Sci Rep 7 16057 (2017)
  14. NMR structure and function of Helicoverpa armigera sterol carrier protein-2, an important insecticidal target from the cotton bollworm. Ma H, Ma Y, Liu X, Dyer DH, Xu P, Liu K, Lan Q, Hong H, Peng J, Peng R. Sci Rep 5 18186 (2015)