PDBsum entry 5xf1

Signaling protein

PDB id: 5xf1

Contents

Protein chains

544 a.a.

496 a.a.

231 a.a.

214 a.a.

Ligands

NAG-NAG ×5

NAG-NAG-NAG

97V ×2

NAG

Waters ×1

PDB id:

5xf1

Name:

Signaling protein

Title:

Structure of the full-length glucagon class b g protein-coupled receptor

Structure:

Glucagon receptor,endolysin,glucagon receptor. Chain: a, b. Fragment: unp residues 27-256,unp residues 2-161,unp residues 260- 432. Synonym: gl-r,lysis protein,lysozyme,muramidase,gl-r. Engineered: yes. Mutation: yes. Other_details: the fusion protein of glucagon receptor (unp residues 27-256), endolysin (unp residues 2-161) and glucagon receptor (unp

Source:

Homo sapiens, enterobacteria phage t4. Human. Organism_taxid: 9606, 10665. Gene: gcgr, e, t4tp126. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108. Homo sapiens. Organism_taxid: 9606. Expressed in: homo sapiens.

Resolution:

3.19Å R-factor: 0.207 R-free: 0.231

Authors:

H.Zhang,A.Qiao,D.Yang,L.Yang,A.Dai,C.De Graaf,S.Reedtz-Runge, V.Dharmarajan,H.Zhang,G.W.Han,T.Grant,R.Sierra,U.Weierstall, G.Nelson,W.Liu,Y.Wu,L.Ma,X.Cai,G.Lin,X.Wu,Z.Geng,Y.Dong,G.Song, P.Griffin,J.Lau,V.Cherezov,H.Yang,M.Hanson,R.Stevens,H.Jiang,M.Wang, Q.Zhao,B.Wu

Key ref:

H.Zhang et al. (2017). Structure of the full-length glucagon class B G-protein-coupled receptor. Nature, 546, 259-264. PubMed id: 28514451

Date:

06-Apr-17 Release date: 24-May-17

Protein chain

P00720  (ENLYS_BPT4) -  Endolysin from Enterobacteria phage T4

Seq: 164 a.a.

Struc: 544 a.a.*

Protein chain

P47871  (GLR_HUMAN) -  Glucagon receptor from Homo sapiens

Seq: 477 a.a.

Struc: 544 a.a.*

Protein chain

P00720  (ENLYS_BPT4) -  Endolysin from Enterobacteria phage T4

Seq: 164 a.a.

Struc: 496 a.a.*

Protein chain

P47871  (GLR_HUMAN) -  Glucagon receptor from Homo sapiens

Seq: 477 a.a.

Struc: 496 a.a.*

Protein chains

No UniProt id for this chain

Struc: 231 a.a.

Protein chains

No UniProt id for this chain

Struc: 214 a.a.

* PDB and UniProt seqs differ at 337 residue positions (black crosses)

Enzyme reactions

• Enzyme class: Chains A, B: E.C.3.2.1.17 - lysozyme.
• Reaction: Hydrolysis of the 1,4-beta-linkages between N-acetyl-D-glucosamine and N-acetylmuramic acid in peptidoglycan heteropolymers of the prokaryotes cell walls.

Nature 546:259-264 (2017)

PubMed id: 28514451

Structure of the full-length glucagon class B G-protein-coupled receptor.

H.Zhang, A.Qiao, D.Yang, L.Yang, A.Dai, C.de Graaf, S.Reedtz-Runge, V.Dharmarajan, H.Zhang, G.W.Han, T.D.Grant, R.G.Sierra, U.Weierstall, G.Nelson, W.Liu, Y.Wu, L.Ma, X.Cai, G.Lin, X.Wu, Z.Geng, Y.Dong, G.Song, P.R.Griffin, J.Lau, V.Cherezov, H.Yang, M.A.Hanson, R.C.Stevens, Q.Zhao, H.Jiang, M.W.Wang, B.Wu.

ABSTRACT

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 Å 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 β-strand conformation, instead of forming an α-helix as observed in the previously solved structure of the GCGR transmembrane domain. The first extracellular loop exhibits a β-hairpin conformation and interacts with the stalk to form a compact β-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.