PDBsum entry 6lml

Signaling protein

PDB id: 6lml

Contents

Protein chains

224 a.a.

306 a.a.

33 a.a.

232 a.a.

29 a.a.

395 a.a.

PDB id:

6lml

Name:

Signaling protein

Title:

Cryo-em structure of the human glucagon receptor in complex with gi1

Structure:

Guanine nucleotide-binding protein g(i) subunit alpha-1. Chain: a. Synonym: adenylate cyclase-inhibiting g alpha protein. Engineered: yes. Mutation: yes. Guanine nucleotide-binding protein g(i)/g(s)/g(t) subunit beta-1. Chain: b. Synonym: transducin beta chain 1.

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: gnai1. Expressed in: unidentified baculovirus. Expression_system_taxid: 10469. Gene: gnb1. Gene: gng2. Mus musculus.

Authors:

A.Qiao,S.Han,X.Li,F.Sun,Q.Zhao,B.Wu

Key ref:

A.Qiao et al. (2020). Structural basis of G_s and G_i recognition by the human glucagon receptor. Science, 367, 1346-1352. PubMed id: 32193322 DOI: 10.1126/science.aaz5346

Date:

26-Dec-19 Release date: 01-Apr-20

Protein chain

P12497  (POL_HV1N5) -  Gag-Pol polyprotein from Human immunodeficiency virus type 1 group M subtype B (isolate NY5)

Seq: 1435 a.a.

Struc: 224 a.a.*

Protein chain

No UniProt id for this chain

Struc: 306 a.a.

Protein chain

No UniProt id for this chain

Struc: 33 a.a.

Protein chain

No UniProt id for this chain

Struc: 232 a.a.

Protein chain

No UniProt id for this chain

Struc: 29 a.a.

Protein chain

No UniProt id for this chain

Struc: 395 a.a.

* PDB and UniProt seqs differ at 203 residue positions (black crosses)

Enzyme reactions

• Enzyme class: Chain A: E.C.3.6.5.- - ?????

DOI no: 10.1126/science.aaz5346

Science 367:1346-1352 (2020)

PubMed id: 32193322

Structural basis of G_s and G_i recognition by the human glucagon receptor.

A.Qiao, S.Han, X.Li, Z.Li, P.Zhao, A.Dai, R.Chang, L.Tai, Q.Tan, X.Chu, L.Ma, T.S.Thorsen, S.Reedtz-Runge, D.Yang, M.W.Wang, P.M.Sexton, D.Wootten, F.Sun, Q.Zhao, B.Wu.

ABSTRACT

Class B G protein-coupled receptors, an important class of therapeutic targets, signal mainly through the G_s class of heterotrimeric G proteins, although they do display some promiscuity in G protein binding. Using cryo-electron microscopy, we determined the structures of the human glucagon receptor (GCGR) bound to glucagon and distinct classes of heterotrimeric G proteins, G_s or G_i1 These two structures adopt a similar open binding cavity to accommodate G_s and G_i1 The G_s binding selectivity of GCGR is explained by a larger interaction interface, but there are specific interactions that affect G_i more than G_s binding. Conformational differences in the receptor intracellular loops were found to be key selectivity determinants. These distinctions in transducer engagement were supported by mutagenesis and functional studies.