A graph-based approach identifies dynamic H-bond communication networks in spike protein S of SARS-CoV-2.
J Struct Biol
; 212(2): 107617, 2020 11 01.
Article
in English
| MEDLINE | ID: covidwho-753204
Preprint
This scientific journal article is probably based on a previously available preprint. It has been identified through a machine matching algorithm, human confirmation is still pending.
See preprint
This scientific journal article is probably based on a previously available preprint. It has been identified through a machine matching algorithm, human confirmation is still pending.
See preprint
ABSTRACT
Corona virus spike protein S is a large homo-trimeric protein anchored in the membrane of the virion particle. Protein S binds to angiotensin-converting-enzyme 2, ACE2, of the host cell, followed by proteolysis of the spike protein, drastic protein conformational change with exposure of the fusion peptide of the virus, and entry of the virion into the host cell. The structural elements that govern conformational plasticity of the spike protein are largely unknown. Here, we present a methodology that relies upon graph and centrality analyses, augmented by bioinformatics, to identify and characterize large H-bond clusters in protein structures. We apply this methodology to protein S ectodomain and find that, in the closed conformation, the three protomers of protein S bring the same contribution to an extensive central network of H-bonds, and contribute symmetrically to a relatively large H-bond cluster at the receptor binding domain, and to a cluster near a protease cleavage site. Markedly different H-bonding at these three clusters in open and pre-fusion conformations suggest dynamic H-bond clusters could facilitate structural plasticity and selection of a protein S protomer for binding to the host receptor, and proteolytic cleavage. From analyses of spike protein sequences we identify patches of histidine and carboxylate groups that could be involved in transient proton binding.
Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Pneumonia, Viral
/
Computer Graphics
/
Coronavirus Infections
/
Peptidyl-Dipeptidase A
/
Protein Interaction Mapping
/
Spike Glycoprotein, Coronavirus
/
Betacoronavirus
Type of study:
Experimental Studies
/
Randomized controlled trials
Limits:
Humans
Language:
English
Journal:
J Struct Biol
Journal subject:
Molecular Biology
Year:
2020
Document Type:
Article
Affiliation country:
J.jsb.2020.107617
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