PDBsum entry 7k8s

Viral protein/immune system

PDB id: 7k8s

Contents

Protein chains

1004 a.a.

125 a.a.

107 a.a.

Ligands

NAG-NAG ×15

NAG ×27

PDB id:

7k8s

Name:

Viral protein/immune system

Title:

Structure of the sars-cov-2 s 2p trimer in complex with the human neutralizing antibody fab fragment, c002 (state 1)

Structure:

Spike glycoprotein. Chain: a, b, c. Synonym: s glycoprotein,e2,peplomer protein. Engineered: yes. C002 fab heavy chain. Chain: h, m, o. Engineered: yes. C002 fab light chain. Chain: l, n, p.

Source:

Severe acute respiratory syndrome coronavirus 2. 2019-ncov. Organism_taxid: 2697049. Gene: s, 2. Expressed in: homo sapiens. Expression_system_taxid: 9606. Expression_system_cell_line: hek293. Homo sapiens.

Authors:

C.O.Barnes,A.G.Malyutin,P.J.Bjorkman

Key ref:

C.O.Barnes et al. (2020). SARS-CoV-2 neutralizing antibody structures inform therapeutic strategies. Nature, 588, 682-687. PubMed id: 33045718 DOI: 10.1016/j.cell.2020.09.037

Date:

27-Sep-20 Release date: 21-Oct-20

Protein chains

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

Seq: 1273 a.a.

Struc: 1004 a.a.*

Protein chains

No UniProt id for this chain

Struc: 125 a.a.

Protein chains

No UniProt id for this chain

Struc: 107 a.a.

* PDB and UniProt seqs differ at 2 residue positions (black crosses)

DOI no: 10.1016/j.cell.2020.09.037

Nature 588:682-687 (2020)

PubMed id: 33045718

SARS-CoV-2 neutralizing antibody structures inform therapeutic strategies.

C.O.Barnes, C.A.Jette, M.E.Abernathy, K.A.Dam, S.R.Esswein, H.B.Gristick, A.G.Malyutin, N.G.Sharaf, K.E.Huey-Tubman, Y.E.Lee, D.F.Robbiani, M.C.Nussenzweig, A.P.West, P.J.Bjorkman.

ABSTRACT

The coronavirus disease 2019 (COVID-19) pandemic presents an urgent health crisis. Human neutralizing antibodies that target the host ACE2 receptor-binding domain (RBD) of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) spike protein^1-5 show promise therapeutically and are being evaluated clinically^6-8. Here, to identify the structural correlates of SARS-CoV-2 neutralization, we solved eight new structures of distinct COVID-19 human neutralizing antibodies⁵ in complex with the SARS-CoV-2 spike trimer or RBD. Structural comparisons allowed us to classify the antibodies into categories: (1) neutralizing antibodies encoded by the VH3-53 gene segment with short CDRH3 loops that block ACE2 and bind only to 'up' RBDs; (2) ACE2-blocking neutralizing antibodies that bind both up and 'down' RBDs and can contact adjacent RBDs; (3) neutralizing antibodies that bind outside the ACE2 site and recognize both up and down RBDs; and (4) previously described antibodies that do not block ACE2 and bind only to up RBDs⁹. Class 2 contained four neutralizing antibodies with epitopes that bridged RBDs, including a VH3-53 antibody that used a long CDRH3 with a hydrophobic tip to bridge between adjacent down RBDs, thereby locking the spike into a closed conformation. Epitope and paratope mapping revealed few interactions with host-derived N-glycans and minor contributions of antibody somatic hypermutations to epitope contacts. Affinity measurements and mapping of naturally occurring and in vitro-selected spike mutants in 3D provided insight into the potential for SARS-CoV-2 to escape from antibodies elicited during infection or delivered therapeutically. These classifications and structural analyses provide rules for assigning current and future human RBD-targeting antibodies into classes, evaluating avidity effects and suggesting combinations for clinical use, and provide insight into immune responses against SARS-CoV-2.