September 17, 2010
Extracellular GPCR Domains of Known X-ray Structure
The simplest way to get at least a portion of a membrane protein structure is to 'chop off' the transmembrane portion and determine the structure of the remaining isolated, non-transmembrane domains. In GPCRs the extracellular portions, sometimes called ectodomains, of class B and class C receptors fold into in such independent domains that retain ligand binding and hence their crystallographic structures have been determined. The most recent addition to this class is the ectodomain complex of the CGRP receptor with bound antagonists, nicely covered in this teaser: RAMP-ing up Class-B GPCR ECD Structural Coverage. The table below lists this and other "Extracellular GPCR domains of known structure."
Table: Extracellular GPCR domains of known structure
| GPCR extracellular domain structure | PDB access code | Resolution | Reference |
|---|---|---|---|
| CGRP receptor extracellular domain, class B ECD complex with RAMP 1 protein and antagonists Olcegepant and Telcagepant |
3N7P 3N7R 3N7S |
2.8 2.9 2.1 |
Ernst ter Haar et al. Crystal Structure of the Ectodomain Complex of the CGRP Receptor, a Class-B GPCR, Reveals the Site of Drug Antagonism Structure, Volume 18, Issue 9, 1083-1093, 2010 |
| Methuselah receptor ectodomain with peptide inhibitor (Drosophila) | 1FJR | 2.3 |
West AP Jr, Llamas LL, Snow PM, Benzer S, Bjorkman PJ. (2001) Crystal structure of the ectodomain of Methuselah, a Drosophila G protein-coupled receptor associated with extended lifespan. Proc.Natl.Acad.Sci.USA 98: 3744-3749 |
| Vasoactive intestinal polypeptide Receptor 2 (human) | 2X57 | 2.1 | To be published |
| Parathyroid hormone receptor (PTH1R) in complex with parathyroid hormone-related protein (PTHrP) | 3H3G | 1.94 |
Pioszak et. al. Structural basis for parathyroid hormone-related protein binding to the parathyroid hormone receptor and design of conformation-selective peptides. (2009) J.Biol.Chem. 284: 28382-28391 |
| GIP (gastric inhibitory polypeptide) receptor in complex with GIP hormone (human) | 2QKH | 1.9 |
Parthier et al. Crystal structure of the incretin-bound extracellular domain of a G protein-coupled receptor (2007) Proc.Natl.Acad.Sci.Usa 104: 13942-13947 |
| FSH (follicle stimulating hormone) receptor in complex with the FSH hormone | 1XWD | 2.92 |
Fan, Q.R., Hendrickson, W.A. Structure of human follicle-stimulating hormone in complex with its receptor. (2005) Nature 433: 269-277 |