Structure of the Full-length glucagon class B G protein-coupled receptorStructure of the Full-length glucagon class B G protein-coupled receptor

Structural highlights

5xf1 is a 6 chain structure with sequence from Escherichia virus T4 and Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 3.19Å
Ligands:,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

ENLYS_BPT4 Endolysin with lysozyme activity that degrades host peptidoglycans and participates with the holin and spanin proteins in the sequential events which lead to the programmed host cell lysis releasing the mature viral particles. Once the holin has permeabilized the host cell membrane, the endolysin can reach the periplasm and break down the peptidoglycan layer.[1] GLR_HUMAN This is a receptor for glucagon which plays a central role in regulating the level of blood glucose by controlling the rate of hepatic glucose production and insulin secretion. The activity of this receptor is mediated by G proteins which activate adenylyl cyclase and also a phosphatidylinositol-calcium second messenger system.

Publication Abstract from PubMed

The human glucagon receptor, GCGR, belongs to the class B G-protein-coupled receptor family and plays a key role in glucose homeostasis and the pathophysiology of type 2 diabetes. Here we report the 3.0 A crystal structure of full-length GCGR containing both the extracellular domain and transmembrane domain in an inactive conformation. The two domains are connected by a 12-residue segment termed the stalk, which adopts a beta-strand conformation, instead of forming an alpha-helix as observed in the previously solved structure of the GCGR transmembrane domain. The first extracellular loop exhibits a beta-hairpin conformation and interacts with the stalk to form a compact beta-sheet structure. Hydrogen-deuterium exchange, disulfide crosslinking and molecular dynamics studies suggest that the stalk and the first extracellular loop have critical roles in modulating peptide ligand binding and receptor activation. These insights into the full-length GCGR structure deepen our understanding of the signalling mechanisms of class B G-protein-coupled receptors.

Structure of the full-length glucagon class B G-protein-coupled receptor.,Zhang H, Qiao A, Yang D, Yang L, Dai A, de Graaf C, Reedtz-Runge S, Dharmarajan V, Zhang H, Han GW, Grant TD, Sierra RG, Weierstall U, Nelson G, Liu W, Wu Y, Ma L, Cai X, Lin G, Wu X, Geng Z, Dong Y, Song G, Griffin PR, Lau J, Cherezov V, Yang H, Hanson MA, Stevens RC, Zhao Q, Jiang H, Wang MW, Wu B Nature. 2017 Jun 8;546(7657):259-264. doi: 10.1038/nature22363. Epub 2017 May 17. PMID:28514451[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

See Also

References

  1. Moussa SH, Kuznetsov V, Tran TA, Sacchettini JC, Young R. Protein determinants of phage T4 lysis inhibition. Protein Sci. 2012 Apr;21(4):571-82. doi: 10.1002/pro.2042. Epub 2012 Mar 2. PMID:22389108 doi:http://dx.doi.org/10.1002/pro.2042
  2. Zhang H, Qiao A, Yang D, Yang L, Dai A, de Graaf C, Reedtz-Runge S, Dharmarajan V, Zhang H, Han GW, Grant TD, Sierra RG, Weierstall U, Nelson G, Liu W, Wu Y, Ma L, Cai X, Lin G, Wu X, Geng Z, Dong Y, Song G, Griffin PR, Lau J, Cherezov V, Yang H, Hanson MA, Stevens RC, Zhao Q, Jiang H, Wang MW, Wu B. Structure of the full-length glucagon class B G-protein-coupled receptor. Nature. 2017 Jun 8;546(7657):259-264. doi: 10.1038/nature22363. Epub 2017 May 17. PMID:28514451 doi:http://dx.doi.org/10.1038/nature22363

5xf1, resolution 3.19Å

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