PDBsum entry 7d3s

Membrane protein

PDB id: 7d3s

Contents

Protein chains

27 a.a.

266 a.a.

230 a.a.

340 a.a.

57 a.a.

128 a.a.

PDB id:

7d3s

Name:

Membrane protein

Title:

Human secr in complex with an engineered gs heterotrimer

Structure:

Secretin. Chain: p. Engineered: yes. Secretin receptor. Chain: r. Synonym: sct-r. Engineered: yes. Guanine nucleotide-binding protein g(s) subunit alpha isoforms short.

Source:

Synthetic: yes. Homo sapiens. Human. Organism_taxid: 9606. Gene: sctr. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108. Gene: gnas, gnas1, gsp. Expressed in: escherichia coli.

Authors:

S.Fukuhara,K.Kobayashi,T.Kusakizako,W.Shihoya,O.Nureki

Key ref:

S.Fukuhara et al. (2020). Structure of the human secretin receptor coupled to an engineered heterotrimeric G protein. Biochem Biophys Res Commun, 533, 861-866. PubMed id: 33008599 DOI: 10.1016/j.bbrc.2020.08.042

Date:

20-Sep-20 Release date: 04-Nov-20

Protein chain

P09683  (SECR_HUMAN) -  Secretin from Homo sapiens

Seq: 121 a.a.

Struc: 27 a.a.

Protein chain

P47872  (SCTR_HUMAN) -  Secretin receptor from Homo sapiens

Seq: 440 a.a.

Struc: 266 a.a.

Protein chain

P63092  (GNAS2_HUMAN) -  Guanine nucleotide-binding protein G(s) subunit alpha isoforms short from Homo sapiens

Seq: 394 a.a.

Struc: 230 a.a.*

Protein chain

P54311  (GBB1_RAT) -  Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 from Rattus norvegicus

Seq: 340 a.a.

Struc: 340 a.a.*

Protein chain

P63212  (GBG2_BOVIN) -  Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 from Bos taurus

Seq: 71 a.a.

Struc: 57 a.a.

Protein chain

No UniProt id for this chain

Struc: 128 a.a.

* PDB and UniProt seqs differ at 7 residue positions (black crosses)

Enzyme reactions

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

DOI no: 10.1016/j.bbrc.2020.08.042

Biochem Biophys Res Commun 533:861-866 (2020)

PubMed id: 33008599

Structure of the human secretin receptor coupled to an engineered heterotrimeric G protein.

S.Fukuhara, K.Kobayashi, T.Kusakizako, W.Iida, M.Kato, W.Shihoya, O.Nureki.

ABSTRACT

Secretin is a gastrointestinal hormone that exerts multiple physiological functions via activation of the secretin receptor (SECR). SECR belongs to the class B G-protein-coupled receptors and is involved in various processes, such as regulation of the pH of the duodenal content, food intake, and water homeostasis. Here, we report a cryo-electron microscopy structure of human SECR bound to secretin and an engineered Gs heterotrimer. The structure revealed the basic architecture of SECR and the secretin binding mode. A structural comparison of the SECR and PAC1R transmembrane domains revealed that transmembrane helices 1 and 2 play a prominent role in secretin recognition. Moreover, the extracellular domain of SECR is perpendicular to the TMD, unlike that of PAC1R. This comparison revealed the diverged peptide recognition mechanisms of these receptors, which belong to the same subgroup. Our structural information will facilitate drug discovery research for clinical applications.