G protein-coupled receptor

From Proteopedia

Revision as of 17:54, 9 October 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
• 3pwh - human A2A adenosine receptor
• 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 - human A2A adenosine receptor in complex with the endogenous agonist adenosine
• 2ydv - human A2A adenosine receptor in complex with synthetic agonist NECA
• 4eiy - human A2A adenosine receptor thermostabilized by replacing its third intracellular loop with apocytochrome b(562)RIL

Histamine H1 receptor

• 3rze - human histamine H1 receptor

Sphingosine 1-phosphate Receptor

• 3v2w,3v2y - human sphingosine 1-phosphate receptor 1 with a bound sphingolipid mimic

Dopamine D3 Receptor

• 3pbl - human Dopamine D3 Receptor + T4 lysozyme insertion in complex with Eticlopride and cholesterol

CXCR4 Chemokine Receptor

• 3odu,3oe0,3oe8,3oe9,3oe6 - human sphingosine 1-phosphate receptor 1 with a bound sphingolipid mimic

Muscarinic M2 receptor

• 3uon - human muscarinic M2 receptor, complexed with an antagonist 3-quinuclidinyl-benzilate

Muscarinic M3 receptor

• 4daj - rat muscarinic M3 receptor, complexed with bronchodilator drug tiotropium

kappa opioid receptor

• 4djh - human kappa opioid receptor, complexed with antagonist JDTic

mu opioid receptor

• 4dkl - mouse mu opioid receptor, complexed with an irreversible morphinan antagonist

delta opioid receptor

• 4ej4 - mouse delta opioid receptor, complexed with naltrindole

nociceptin/orphanin FQ receptor

• 4ea3 - human nociceptin/orphanin FQ receptor, complexed with a peptide mimetic antagonist compound 24

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.
• GPCR Network site with tracking chart of ongoing structural programs
• The blog of the Computational Chemical Biology group at the EMBL-EBI does an excellent job tracking the new GPCR structures as they are emerging.
• Emerald Biosystems Blog that features solved structures and on another page features techniques and amounts needed for crystallization of a number of them.
• A 2012 article from Scripps Research Institute that covers a lot of history of solving the structures of GPCRs and their importance.
• 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.