Solution Structure of the Second Extracellular Loop of Human Thromboxane A2 Receptor

• DOI: 10.1021/bi001867c
• Publication Date: 2002-07-26T06:08:25Z
• Authors: Ke-He Ruan; Shui-Ping So; Jiaxin Wu; Dawei Li; Aimin Huang; Jennifer Kung
• Keywords: Models, Molecular; 0303 health sciences; Protein Conformation; Circular Dichroism; Receptors, Thromboxane; Ligands; Peptide Fragments; Protein Structure, Secondary; Protein Structure, Tertiary; Solutions; Structure-Activity Relationship; Thromboxane A2; 03 medical and health sciences; Humans; Extracellular Space; Nuclear Magnetic Resonance, Biomolecular

Thromboxane A2 receptor (TP receptor), a prostanoid receptor, belongs to the G protein-coupled family, composed of three intracellular loops and extracellular connecting seven transmembrane helices. The highly conserved domains receptors were found in second loop (eLP2), which was proposed be involved ligand recognition. 3D structure eLP2 would help further explain binding mechanism. Analysis human TP model generated from molecular modeling based on bacteriorhodopsin crystallographic indicated that about 12−14 Å separates N- C-termini extra- loops. Synthetic peptides whose termini are constrained this separation presumably more likely mimic native than corresponding region peptide with unrestricted ends. To test new concept, (residues 173−193) has been made connected by homocysteine disulfide bond. Through 2D nuclear magnetic resonance (NMR) experiments, complete 1H NMR assignments, structural construction, overall determined. shows two β-turns at residues 180 185. distance between shown is 14.2 Å, matched (14.5 Å) helices model. This suggests approach using greatly increases likelihood solving whole structures receptor. may also useful studies extramembrane other receptors.