PDBsum entry 7kec

Viral protein

PDB id: 7kec

Contents

Protein chains

966 a.a.

Ligands

NAG-NAG ×12

NAG ×33

PDB id:

7kec

Name:

Viral protein

Title:

Sars-cov-2 d614g 1-rbd-up spike protein trimer without the p986-p987 stabilizing mutations (s-gsas-d614g sub-classification)

Structure:

Spike glycoprotein. Chain: a, b, c. Synonym: s glycoprotein,e2,peplomer protein. Engineered: yes. Mutation: yes

Source:

Severe acute respiratory syndrome coronavirus 2. 2019-ncov. Organism_taxid: 2697049. Gene: s, 2. Expressed in: homo sapiens. Expression_system_taxid: 9606

Authors:

S.Gobeil,P.Acharya

Key ref:

S.M.Gobeil et al. (2021). D614G Mutation Alters SARS-CoV-2 Spike Conformation and Enhances Protease Cleavage at the S1/S2 Junction. Cell Rep, 34, 108630. PubMed id: 33417835

Date:

10-Oct-20 Release date: 04-Nov-20

Protein chains

P0DTC2  (SPIKE_SARS2) -  Spike glycoprotein from Severe acute respiratory syndrome coronavirus 2

Seq: 1273 a.a.

Struc: 966 a.a.*

* PDB and UniProt seqs differ at 1 residue position (black cross)

Cell Rep 34:108630 (2021)

PubMed id: 33417835

D614G Mutation Alters SARS-CoV-2 Spike Conformation and Enhances Protease Cleavage at the S1/S2 Junction.

S.M.Gobeil, K.Janowska, S.McDowell, K.Mansouri, R.Parks, K.Manne, V.Stalls, M.F.Kopp, R.Henderson, R.J.Edwards, B.F.Haynes, P.Acharya.

ABSTRACT

The severe acute respiratory coronavirus 2 (SARS-CoV-2) spike (S) protein is the target of vaccine design efforts to end the coronavirus disease 2019 (COVID-19) pandemic. Despite a low mutation rate, isolates with the D614G substitution in the S protein appeared early during the pandemic and are now the dominant form worldwide. Here, we explore S conformational changes and the effects of the D614G mutation on a soluble S ectodomain construct. Cryoelectron microscopy (cryo-EM) structures reveal altered receptor binding domain (RBD) disposition; antigenicity and proteolysis experiments reveal structural changes and enhanced furin cleavage efficiency of the G614 variant. Furthermore, furin cleavage alters the up/down ratio of the RBDs in the G614 S ectodomain, demonstrating an allosteric effect on RBD positioning triggered by changes in the SD2 region, which harbors residue 614 and the furin cleavage site. Our results elucidate SARS-CoV-2 S conformational landscape and allostery and have implications for vaccine design.