PDBsum entry 7knh

Hydrolase/viral protein

PDB id: 7knh

Contents

Protein chains

1007 a.a.

596 a.a.

Ligands

NAG-NAG ×4

NAG ×48

PDB id:

7knh

Name:

Hydrolase/viral protein

Title:

Cryo-em structure of double ace2-bound sars-cov-2 trimer spike at ph 5.5

Structure:

Spike glycoprotein. Chain: c, a, b. Synonym: s glycoprotein,e2,peplomer protein,sars-cov-2 spike glycoprotein. Engineered: yes. Angiotensin-converting enzyme 2. Chain: e, d. Synonym: ace-related carboxypeptidase,angiotensin-converting enzyme homolog,aceh,metalloprotease mprot15.

Source:

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

Authors:

J.Gorman,M.Rapp,P.D.Kwong,L.Shapiro

Key ref:

T.Zhou et al. (2020). Cryo-EM Structures of SARS-CoV-2 Spike without and with ACE2 Reveal a pH-Dependent Switch to Mediate Endosomal Positioning of Receptor-Binding Domains. Cell Host Microbe, 28, 867. PubMed id: 33271067

Date:

04-Nov-20 Release date: 16-Dec-20

Protein chains

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

Seq: 1273 a.a.

Struc: 1007 a.a.*

Protein chains

Q9BYF1  (ACE2_HUMAN) -  Angiotensin-converting enzyme 2 from Homo sapiens

Seq: 805 a.a.

Struc: 596 a.a.

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

Enzyme reactions

• Enzyme class 1: Chains E, D: E.C.3.4.17.- - ?????
• Enzyme class 2: Chains E, D: E.C.3.4.17.23 - angiotensin-converting enzyme 2.
• Reaction: angiotensin II + H2O = angiotensin-^1-7 + L-phenylalanine

angiotensin II + H2O = angiotensin-(1-7) + L-phenylalanine (Bound ligand (Het Group name = NAG) matches with 44.44% similarity)

Note, where more than one E.C. class is given (as above), each may correspond to a different protein domain or, in the case of polyprotein precursors, to a different mature protein.

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

Added reference

Cell Host Microbe 28:867 (2020)

PubMed id: 33271067

Cryo-EM Structures of SARS-CoV-2 Spike without and with ACE2 Reveal a pH-Dependent Switch to Mediate Endosomal Positioning of Receptor-Binding Domains.

T.Zhou, Y.Tsybovsky, J.Gorman, M.Rapp, G.Cerutti, G.Y.Chuang, P.S.Katsamba, J.M.Sampson, A.Schön, J.Bimela, J.C.Boyington, A.Nazzari, A.S.Olia, W.Shi, M.Sastry, T.Stephens, J.Stuckey, I.T.Teng, P.Wang, S.Wang, B.Zhang, R.A.Friesner, D.D.Ho, J.R.Mascola, L.Shapiro, P.D.Kwong.

ABSTRACT

The SARS-CoV-2 spike employs mobile receptor-binding domains (RBDs) to engage the human ACE2 receptor and to facilitate virus entry, which can occur through low-pH-endosomal pathways. To understand how ACE2 binding and low pH affect spike conformation, we determined cryo-electron microscopy structures-at serological and endosomal pH-delineating spike recognition of up to three ACE2 molecules. RBDs freely adopted "up" conformations required for ACE2 interaction, primarily through RBD movement combined with smaller alterations in neighboring domains. In the absence of ACE2, single-RBD-up conformations dominated at pH 5.5, resolving into a solitary all-down conformation at lower pH. Notably, a pH-dependent refolding region (residues 824-858) at the spike-interdomain interface displayed dramatic structural rearrangements and mediated RBD positioning through coordinated movements of the entire trimer apex. These structures provide a foundation for understanding prefusion-spike mechanics governing endosomal entry; we suggest that the low pH all-down conformation potentially facilitates immune evasion from RBD-up binding antibody.