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Molecular Mechanisms of Ligand Interaction with the Gonadotropin-Releasing Hormone Receptor

Fishberg Research Center in Neurobiology (S.C.S.), Departments of Neurology (S.C.S.), Physiology and Biophysics (H.W.), and Pharmacology (H. W.), Mount Sinai School of Medicine, New York, New York 10029; and Medical Research Council Regulatory Peptides Unit (R.P.M.), Departments of Chemical Pathology (R.P.M.) and Medicine (R.P.M.), University of Cape Town Medical School, Observatory 7925, South Africa

I. Introduction

II. Amino Acid Sequences of GnRH Receptors

A. GnRH receptor cDNAs

B. General structural features

C. Covalent modifications

D. Gene structure

III. Structure-Activity Relations of GnRH Peptides

A. Overview

B. Comparative structures and activities of vertebrate GnRHs

C. Roles of individual amino acids in GnRH activity at the mammalian receptor

D. Conclusions from peptide structure-activity data

IV. Structure and Conformation of GnRH and Its Analogs

A. Early studies of GnRH conformation

B. Integrated computational and experimental studies

C. Exploration of the entire conformation space of GnRH analogs

V. Functional Structure of the Receptor and Ligand-Receptor Complex

A. Extracellular domains

B. Helix domains

C. Intracellular loop domains

D. Computational modeling of three-dimensional receptor structure

VI. Conclusions