Molecular characterization and homology modeling of liver X receptor in Asian seabass, Lates calcarifer: predicted functions in reproduction and lipid metabolism.

ABSTRACT

Liver X receptor (LXR) is a ligand-activated transcription factor that plays vital roles in maintaining cholesterol and lipid homeostasis. Much work has been done on mammalian LXRs, but the role of LXR in fish remains unclear. In the present study, LXR gene was identified from adult Asian seabass, Lates calcarifer, and its predicted protein structure was docked with several cholesterol derivatives at the binding site. The LXR cDNA consisted of 1495 bp encoding a putative LXR protein of 494 amino acids. The Asian seabass LXR retained many important structural features found in LXRs of other fishes and mammals, such as putative signal peptide, activation function-1 (AF-1) domain, DNA-binding domain (DBD), ligand-binding domain (LBD), activation function-2 (AF-2) domain, and eight conserved cysteine residues. The deduced amino acid sequence of LXR shared significant identity with those of other species ranging from 65.7 to 95.8%. The homology modeling and in silico molecular docking demonstrated that Asian seabass LXR could interact with cholesterol derivatives at amino acid residues Phe274 and Ile312. Real-time PCR further revealed that LXR transcripts are ubiquitously expressed in all tissues examined, with the highest levels detected in the gonad followed by the liver. Given the well-known importance of cholesterol-mediated signaling in these tissues, Asian seabass LXR may reasonably be involved in reproduction and lipid metabolism.