4L6R

Structure of the class B human glucagon G protein coupled receptor

Summary for 4L6R

• Entry DOI: 10.2210/pdb4l6r/pdb
• Descriptor: Soluble cytochrome b562 and Glucagon receptor chimera, DI(HYDROXYETHYL)ETHER (2 entities in total)
• Functional Keywords: human glucagon receptor, diabetes, gpcr network, psi-biology, membrane protein, novel protein engineering, structural genomics, protein structure initiative, gpcr, membrane
• Biological source: Escherichia coli (human); More
• Cellular location: Cell membrane ; Multi-pass membrane protein : P47871
• Total number of polymer chains: 1
• Total formula weight: 48256.96

Authors

Siu, F.Y.,He, M.,de Graaf, C.,Han, G.W.,Yang, D.,Zhang, Z.,Zhou, C.,Xu, Q.,Wacker, D.,Joseph, J.S.,Liu, W.,Lau, J.,Cherezov, V.,Katritch, V.,Wang, M.W.,Stevens, R.C.,GPCR Network (GPCR) (deposition date: 2013-06-12, release date: 2013-07-24, Last modification date: 2024-10-30)

Primary citation

Siu, F.Y.,He, M.,de Graaf, C.,Han, G.W.,Yang, D.,Zhang, Z.,Zhou, C.,Xu, Q.,Wacker, D.,Joseph, J.S.,Liu, W.,Lau, J.,Cherezov, V.,Katritch, V.,Wang, M.W.,Stevens, R.C.
Structure of the human glucagon class B G-protein-coupled receptor.
Nature, 499:444-449, 2013

PubMed Abstract: Binding of the glucagon peptide to the glucagon receptor (GCGR) triggers the release of glucose from the liver during fasting; thus GCGR plays an important role in glucose homeostasis. Here we report the crystal structure of the seven transmembrane helical domain of human GCGR at 3.4 Å resolution, complemented by extensive site-specific mutagenesis, and a hybrid model of glucagon bound to GCGR to understand the molecular recognition of the receptor for its native ligand. Beyond the shared seven transmembrane fold, the GCGR transmembrane domain deviates from class A G-protein-coupled receptors with a large ligand-binding pocket and the first transmembrane helix having a 'stalk' region that extends three alpha-helical turns above the plane of the membrane. The stalk positions the extracellular domain (~12 kilodaltons) relative to the membrane to form the glucagon-binding site that captures the peptide and facilitates the insertion of glucagon's amino terminus into the seven transmembrane domain.

PubMed: 23863937
DOI: 10.1038/nature12393

Experimental method

X-RAY DIFFRACTION (3.3 Å)