Crystal Structure of Rhodopsin: A G-Protein-Coupled Receptor

Abstract

Shedding light on GPCRs: The crystal structure of rhodopsin, determined at 2.8 Å resolution, shows the major molecular structural features characteristic of G‐protein‐coupled receptors (see figure). The seven transmembrane helices are aligned roughly perpendicular to the membrane plane, with the binding surface for G proteins located on the cytoplasmic surface. The retinal chromophore important for photon absorption in this vision system protein is completely buried in the protein. The structure of the ground state molecule provides a base for understanding the structural and functional ramifications associated with signal transduction in the retina.

Structural determinants for selective recognition of peptide ligands for endothelin receptor subtypes ETAand ETB

“…The 4 L epitope of peptide ligands is highly conserved in agonists and antagonists (Table 3). Owing to the size of the peptide ligands, the 4 L epitope interacts in our structure models within the ‘classic’ GPCR binding site of small ligands consisting of TMH3–660–65 as well as in the recently described binding site between TMH2, ‐3 and ‐766–68. This orientation is in agreement with data on the interaction of peptide ligands in endothelin receptors17.…”

Structural determinants for selective recognition of peptide ligands for endothelin receptor subtypes ETAand ETB

“…The 4 L epitope of peptide ligands is highly conserved in agonists and antagonists (Table 3). Owing to the size of the peptide ligands, the 4 L epitope interacts in our structure models within the ‘classic’ GPCR binding site of small ligands consisting of TMH3–660–65 as well as in the recently described binding site between TMH2, ‐3 and ‐766–68. This orientation is in agreement with data on the interaction of peptide ligands in endothelin receptors17.…”

Understanding the regulation mechanisms of PAF receptor by agonists and antagonists: Molecular modeling and molecular dynamics simulation studies

“…This is in agreement with the proposal of Ishii et al,13 that the three histidine residues might be directly involved in PAF binding. In addition, the binding mode of PAF to PAFR shares some similarity with that of retinal in BRHO in which the β‐ionone ring of the chromophore occupies the central core and the polyene moiety extends towards helices I, II, III and VII 16–18. As expected, GB [Fig.…”

A continued saga of Boc5, the first non-peptidic glucagon-like peptide-1 receptor agonist with in vivo activities

“…The unique structural architecture and activation mechanism of GPCRs are pivotal factors in this issue. Little secondary structure information is available, and rational drug design has to rely on low homology template modeling of rhodopsin [33] . High resolution crystal structures of GPCRs will certainly expand our understanding of how a ligand gains access to and binds within the receptor binding pocket and finally guide the structure-based drug design [34] .…”

Structural determinants for selective recognition of peptide ligands for endothelin receptor subtypes ETAand ETB

“…The 4 L epitope of peptide ligands is highly conserved in agonists and antagonists (Table 3). Owing to the size of the peptide ligands, the 4 L epitope interacts in our structure models within the ‘classic’ GPCR binding site of small ligands consisting of TMH3–660–65 as well as in the recently described binding site between TMH2, ‐3 and ‐766–68. This orientation is in agreement with data on the interaction of peptide ligands in endothelin receptors17.…”

Understanding the regulation mechanisms of PAF receptor by agonists and antagonists: Molecular modeling and molecular dynamics simulation studies

“…This is in agreement with the proposal of Ishii et al,13 that the three histidine residues might be directly involved in PAF binding. In addition, the binding mode of PAF to PAFR shares some similarity with that of retinal in BRHO in which the β‐ionone ring of the chromophore occupies the central core and the polyene moiety extends towards helices I, II, III and VII 16–18. As expected, GB [Fig.…”

A continued saga of Boc5, the first non-peptidic glucagon-like peptide-1 receptor agonist with in vivo activities

“…The unique structural architecture and activation mechanism of GPCRs are pivotal factors in this issue. Little secondary structure information is available, and rational drug design has to rely on low homology template modeling of rhodopsin [33] . High resolution crystal structures of GPCRs will certainly expand our understanding of how a ligand gains access to and binds within the receptor binding pocket and finally guide the structure-based drug design [34] .…”

Structural determinants for selective recognition of peptide ligands for endothelin receptor subtypes ETAand ETB

“…The 4 L epitope of peptide ligands is highly conserved in agonists and antagonists (Table 3). Owing to the size of the peptide ligands, the 4 L epitope interacts in our structure models within the ‘classic’ GPCR binding site of small ligands consisting of TMH3–660–65 as well as in the recently described binding site between TMH2, ‐3 and ‐766–68. This orientation is in agreement with data on the interaction of peptide ligands in endothelin receptors17.…”

Understanding the regulation mechanisms of PAF receptor by agonists and antagonists: Molecular modeling and molecular dynamics simulation studies

“…This is in agreement with the proposal of Ishii et al,13 that the three histidine residues might be directly involved in PAF binding. In addition, the binding mode of PAF to PAFR shares some similarity with that of retinal in BRHO in which the β‐ionone ring of the chromophore occupies the central core and the polyene moiety extends towards helices I, II, III and VII 16–18. As expected, GB [Fig.…”

A continued saga of Boc5, the first non-peptidic glucagon-like peptide-1 receptor agonist with in vivo activities

“…The unique structural architecture and activation mechanism of GPCRs are pivotal factors in this issue. Little secondary structure information is available, and rational drug design has to rely on low homology template modeling of rhodopsin [33] . High resolution crystal structures of GPCRs will certainly expand our understanding of how a ligand gains access to and binds within the receptor binding pocket and finally guide the structure-based drug design [34] .…”