G protein-coupled receptor

From Proteopedia

Revision as of 21:27, 26 September 2012

G protein-coupled receptors, often abbreviated GPCRs, are an abundant superamily of proteins also known as seven-transmembrane domain receptors, 7TM receptors, heptahelical receptors, serpentine receptor, and G protein-linked receptors (GPLRs). G protein-coupled receptors are cell surface signalling proteins involved in many physiological functions and in multiple diseases. They are also the target of the majority of all modern medicinal drugs^[1][2].

Illustrating their importance and the largesse of the superfamily, there are roughly 800 known members of the superfamily in the human genome alone. Members are further subclassified into one of five families of GPCRs^[3].

Rhodopsin shares similar membrane topology with the members of the superfamily, specifically family A of the G protein-coupled receptors which include the seven transmembrane helices, an extracellular N terminus and cytoplasmic C terminus^[4].

3D Structures of G protein-coupled receptors

Rhodopsins

Rhodopsins are listed individually in a section on the Rhodopsin topic page

3D structures in Rhodopsin.

β2 adrenergic receptor

• A topic page concerning the Beta-2 Adrenergic Receptor

3D structures in Adrenergic receptor.

β1 adrenergic receptor

3D structures in Adrenergic receptor.

A2A adenosine receptor

• 3eml - human A2A adenosine receptor bound to antagaonist ZM241385
• 3qak - human A2A adenosine receptor bound to an agonist UK-432097
• 3vg9 - human A2A adenosine receptor in complex with a mouse monoclonal-antibody Fab fragment, Fab2838
• 3vga - human A2A adenosine receptor in complex with a mouse monoclonal-antibody Fab fragment, Fab2838
• 2yd0,2ydv - human A2A adenosine receptor in complex agonists

Histamine H1 receptor

• 3rze - human histamine H1 receptor

3kj6 3ny8 3ny9 3nya 1bl1 1d6g 1ddv 1dep

1edw 1edx 1ewk 1ewt 1ewv 1f88 1fdf 1fjr 1gzm 1hll 1ho9 1hod 1hof 1hzn

References and Notes

1. ↑ Overington JP, Al-Lazikani B, Hopkins AL. How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. PMID:17139284 doi:10.1038/nrd2199
2. ↑ Peeters MC, van Westen GJ, Li Q, IJzerman AP. Importance of the extracellular loops in G protein-coupled receptors for ligand recognition and receptor activation. Trends Pharmacol Sci. 2011 Jan;32(1):35-42. PMID:21075459 doi:10.1016/j.tips.2010.10.001
3. ↑ Millar RP, Newton CL. The year in G protein-coupled receptor research. Mol Endocrinol. 2010 Jan;24(1):261-74. Epub 2009 Dec 17. PMID:20019124 doi:10.1210/me.2009-0473
4. ↑ Kristiansen K. Molecular mechanisms of ligand binding, signaling, and regulation within the superfamily of G-protein-coupled receptors: molecular modeling and mutagenesis approaches to receptor structure and function. Pharmacol Ther. 2004 Jul;103(1):21-80. PMID:15251227 doi:10.1016/j.pharmthera.2004.05.002

See Also

• Rhodopsin
• Pharmaceutical Drugs
• Membrane proteins
• Hormone

Additional Literature

• PMID: xxxx

External Resources

• The April 2008 RCSB PDB Molecule of the Month feature on Adrenergic Receptors by David S. Goodsell is 10.2210/rcsb_pdb/mom_2008_4.
• GPCRDB: database contains sequences, ligand binding constants and mutations, in addition GPCR multiple sequence alignments and homology models. Moreover, the site contains useful structure files where lysozyme and other inserts commonly used in the difficult process of crystallizing these transmembrane structures are removed.
• Blog that features solved structures and on another page features techniques and amounts needed for crystallization of a number of them.
• tinyGRAP GPCR mutant database
• GPCR-OKB: GPCR Oligomerization Knowledge Base
• GPCR Natural Variants Database (NaVa)
• The PRED-GPCR server for GPCR recognition and family classification.