Differences in the structure and dynamics of the apo- and palmitate- ligated forms of Aedes aegypti sterol carrier protein 2 (AeSCP-2)
Autor(es): Singarapu, Kiran K.; Radek, James T.; Tonelli, Marco; Markley, John L.; Lan, Que
Resumo: Sterol carrier protein-2 (SCP-2) is a nonspecific lipid-binding protein expressed ubiquitously in most organisms. Knockdown of SCP-2 expression in mosquitoes has been shown to result in high mortality in developing adults and significantly lowered fertility. Thus, it is of interest to determine the structure of mosquito SCP-2 and to identify its mechanism of lipid binding. We report here high quality three-dimensional solution structures of SCP-2 from Aedes aegypti determined by NMR spectroscopy in its ligand-free state (AeSCP-2) and in complex with palmitate. Both structures have a similar mixed a/b fold consisting of a five-stranded b-sheet and four a-helices arranged on one side of the b-sheet. Ligand-free AeSCP-2 exhibited regions of structural heterogeneity, as evidenced by multiple two-dimensional super(15)N heteronuclear single-quantum coherence peaks for certain amino acids; this heterogeneity disappeared upon complex formation with palmitate. The binding of palmitate to AeSCP-2 was found to decrease the backbone mobility of the protein but not to alter its secondary structure. Complex formation is accompanied by chemical shift differences and a loss of mobility for residues in the loop between helix aI and strand bA. The structural differences between the aI and bA of the mosquito and the vertebrate SCP-2s may explain the differential specificity (insect versus vertebrate) of chemical inhibitors of the mosquito SCP-2.
Palavras-Chave: Fertility; Specificity; Sterols; Inhibitors; Proteins; Pest control; Nitrogen isotopes; Aquatic insects; Mortality causes; Mortality; Lipid-binding protein; Amino acids; Mobility; sterol carrier proteins; Magnetic resonance spectroscopy; Palmitic acid; Electrophoretic mobility; Aedes aegypti
Imprenta: Journal of Biological Chemistry, v. 285, n. 22, p. 17046-17053, 2010.
Descritores: Aedes aegypti - Molecular Structure ; Aedes aegypti - Proteins
Data de publicação: 2010
