TY - JOUR
T1 - Thyrotropin-releasing hormone and its receptors - A hypothesis for binding and receptor activation
AU - Engel, Stanislav
AU - Gershengorn, Marvin C.
N1 - Funding Information:
This work was supported in part by the Intramural Research Program of the NIH, NIDDK.
PY - 2007/2/1
Y1 - 2007/2/1
N2 - Thyrotropin-releasing hormone (TRH), a tripeptide, exerts its biological effects through stimulation of cell-surface receptors, TRH-R, belonging to the superfamily of G protein-coupled receptors (GPCR). Because of the intermediate size of TRH, it is smaller than polypeptide ligands that interact at GPCR ectodomains and larger than biogenic amines, which interact within GPCR transmembrane domains (TMD), the TRH/TRH-R complex probably shares properties of these 2 extremes, representing a unique system to study GPCR/ligand interactions. In this review, we summarize the current knowledge of the structure-activity relationships in the TRH/TRH-R system. Based on experimental data and the structural information acquired from computer simulations, we formulate a working hypothesis to describe the molecular events underlying the processes of TRH binding and TRH-R activation. This hypothesis represents a starting point for understanding the biology of the TRH/TRH-R system on a molecular level and provides a basis for potential design of new potent and selective modulators of TRH-R's activity.
AB - Thyrotropin-releasing hormone (TRH), a tripeptide, exerts its biological effects through stimulation of cell-surface receptors, TRH-R, belonging to the superfamily of G protein-coupled receptors (GPCR). Because of the intermediate size of TRH, it is smaller than polypeptide ligands that interact at GPCR ectodomains and larger than biogenic amines, which interact within GPCR transmembrane domains (TMD), the TRH/TRH-R complex probably shares properties of these 2 extremes, representing a unique system to study GPCR/ligand interactions. In this review, we summarize the current knowledge of the structure-activity relationships in the TRH/TRH-R system. Based on experimental data and the structural information acquired from computer simulations, we formulate a working hypothesis to describe the molecular events underlying the processes of TRH binding and TRH-R activation. This hypothesis represents a starting point for understanding the biology of the TRH/TRH-R system on a molecular level and provides a basis for potential design of new potent and selective modulators of TRH-R's activity.
KW - Active conformation
KW - Agonist
KW - GPCR activation
KW - Ligand binding
KW - Structure-activity relationships
KW - TRH receptor
UR - http://www.scopus.com/inward/record.url?scp=33846428430&partnerID=8YFLogxK
U2 - 10.1016/j.pharmthera.2006.09.004
DO - 10.1016/j.pharmthera.2006.09.004
M3 - Review article
C2 - 17123625
AN - SCOPUS:33846428430
SN - 0163-7258
VL - 113
SP - 410
EP - 419
JO - Pharmacology and Therapeutics
JF - Pharmacology and Therapeutics
IS - 2
ER -