Coupling interaction between thromboxane A2 receptor and alpha-13 subunit of guanine nucleotide-binding protein.
G protein-coupled receptors (GPCRs) form a large superfamily of membrane proteins that play an essential role in modulating many vital physiological events, such as cell communication, neurotransmission, sensory perception, and chemotaxis. Understanding of the 3D (dimensional) structures of these receptors and their binding interactions with G proteins will help in the design of drugs for the treatment of GPCR-related diseases. By means of the approach of structural bioinformatics, the 3D structures of human alpha-13 subunit of guanine nucleotide-binding protein (G alpha 13) and human thromboxane A2 (TXA2) receptor were developed. The former plays an important role in the control of cell growth that may serve as a prototypical G protein; the latter is a target for nitric oxide-mediated desensitization that may serve as a prototypical GPCR. On the basis of the 3D models, their coupling interactions were investigated via docking studies. It has been found that the two proteins are coupled with each other mainly through the interaction between the minigene of G alpha 13 and the 3rd intracellular loop of the TXA2 receptor, consistent with the existing deduction in the literatures. However, it has also been observed via a close view that some residues of the TXA2 receptor that are sequentially far away but spatially quite close to the loop region are also involved in forming hydrogen bonds with the minigene of G alpha 13. These findings may provide useful information for conducting mutagenesis and reveal the molecular mechanism how the human TXA2 receptor interact with G alpha 13 to activate intracellular signaling. The findings may also provide useful insights for stimulating new therapeutic approaches by manipulating the interaction of the receptor with the relevant G proteins.
Chou
Kuo-Chen
KC
Gordon Life Science Institute, 13784 Torrey Del Mar, San Diego, CA 92130, USA. kchou@san.rr.com
D000495:Allosteric Site; D000595:Amino Acid Sequence; D000818:Animals; D002417:Cattle; D019295:Computational Biology; D018360:Crystallography, X-Ray; D044365:GTP-Binding Protein alpha Subunits, G12-G13 / Q000737:chemistry*; D006801:Humans; D006860:Hydrogen Bonding; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016296:Mutagenesis; D009569:Nitric Oxide / Q000737:chemistry; D011485:Protein Binding; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D044244:Receptors, Thromboxane A2, Prostaglandin H2 / Q000737:chemistry*; D012243:Rhodopsin / Q000737:chemistry; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction
D044244:Receptors, Thromboxane A2, Prostaglandin H2; D009569:Nitric Oxide; D012243:Rhodopsin; D044365:GTP-Binding Protein alpha Subunits, G12-G13