Mutational Analysis of the Relative Orientation of Transmembrane Helices I and VII in G Protein-coupled Receptors

The structures of the seven transmembrane helices of G-protein-coupled receptors are critically involved in many aspects of these receptors, such as receptor stability, ligand docking, and molecular function. Most of the previous multitemplate approaches have built a “super” template with very little merging of aligned fragments from different templates. Here, we present a parallelized multitemplate approach, patGPCR, to predict the 3D structures of transmembrane helices of G-protein-coupled receptors. patGPCR, which employs a bundle-packing related energy function that extends on the RosettaMem energy, parallelizes eight pipelines for transmembrane helix refinement and exchanges the optimized helix structures from multiple templates. We have investigated the performance of patGPCR on a test set containing eight determined G-protein-coupled receptors. The results indicate that patGPCR improves the TM RMSD of the predicted models by 33.64% on average against a single-template method. Compared with other homology approaches, the best models for five of the eight targets built by patGPCR had a lower TM RMSD than that obtained from SWISS-MODEL; patGPCR also showed lower average TM RMSD than single-template and multiple-template MODELLER.

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Functional role of proline and tryptophan residues highly conserved among G protein-coupled receptors studied by mutational analysis of the m3 muscarinic receptor.

The EMBO Journal ◽

10.1002/j.1460-2075.1993.tb05661.x ◽

1993 ◽

Vol 12 (1) ◽

pp. 331-338 ◽

Cited By ~ 106

Author(s):

J. Wess ◽

S. Nanavati ◽

Z. Vogel ◽

R. Maggio

Keyword(s):

G Protein ◽

Muscarinic Receptor ◽

Functional Role ◽

Mutational Analysis ◽

G Protein Coupled Receptors ◽

Tryptophan Residues ◽

M3 Muscarinic Receptor ◽

G Protein Coupled

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The arrangement of the transmembrane helices in the secretin receptor family of G-protein-coupled receptors

FEBS Letters ◽

10.1016/s0014-5793(97)00546-2 ◽

1997 ◽

Vol 409 (3) ◽

pp. 431-436 ◽

Cited By ~ 55

Author(s):

Dan Donnelly

Keyword(s):

G Protein ◽

G Protein Coupled Receptors ◽

Transmembrane Helices ◽

Secretin Receptor ◽

G Protein Coupled ◽

Receptor Family

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The structure of bacteriorhodopsin and its relevance to the visual opsins and other seven-helix G-protein coupled receptors

Philosophical Transactions of the Royal Society of London Series B Biological Sciences ◽

10.1098/rstb.1990.0019 ◽

1990 ◽

Vol 326 (1236) ◽

pp. 379-389 ◽

Cited By ~ 81

Keyword(s):

G Protein ◽

Chloride Ion ◽

G Protein Coupled Receptors ◽

Three Dimensions ◽

Ion Pump ◽

Direct Sequence ◽

Transmembrane Helices ◽

Visual Transduction ◽

Receptor Proteins ◽

G Protein Coupled

Bacteriorhodopsin is a light-driven hydrogen-ion pump whose structure is known to about 6.0 Å in three dimensions and 2.8 Å in projection. It consists of seven transmembrane helices surrounding the chromophore, retinal. Halorhodopsin is a second member of the same family of membrane proteins, both of them from the cell membrane of halobacteria. Halorhodopsin is a light-driven chloride-ion pump but has very close homology to bacteriorhodopsin, especially around the retinal. In contrast, the visual opsins that are responsible for the primary step in visual transduction in all eukaryotes from Drosophila upwards, form a separate family with no direct sequence homology to the bacteriorhodopsin family. The visual opsin family now includes about 15 other receptor proteins, all of which activate G-protein cascades, including the β-adrenergic receptor as well as several others. Despite the lack of clear relations at the level of amino acid sequence, there are topographical similarities between the bacteriorhodopsin and the visual opsin families in the nature and site of chromophore attachment, the number of transmembrane helices and the positions of the amino and carboxyl termini in the membrane. These suggest that if the two were at one time closely related, they have diverged too far to have sequences that are detectably similar.

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