ACE2 Peptide Fragment Interaction with Different S1 Protein Sites.

Kuznetsov A, Arukuusk P, Härk H, Juronen E, Ustav M, Langel Ü, Järv J

Int J Pept Res Ther 28 (1) 7 [2021-12-01; online 2021-12-01]

We study the effect of the peptide QAKTFLDKFNHEAEDLFYQ on the kinetics of the SARS-CoV-2 spike protein S1 binding to angiotensin-converting enzyme 2 (ACE2), with the aim to characterize the interaction mechanism of the SARS-CoV2 virus with its host cell. This peptide corresponds to the sequence 24-42 of the ACE2 α1 domain, which marks the binding site for the S1 protein. The kinetics of S1-ACE2 complex formation was measured in the presence of various concentrations of the peptide using bio-layer interferometry. Formation of the S1-ACE2 complex was inhibited by the peptide in cases where it was preincubated with S1 protein before the binding experiment. The kinetic analysis of S1-ACE2 complex dissociation revealed that preincubation stabilized this complex, and this effect was dependent on the peptide concentration as well as the preincubation time. The results point to the formation of the ternary complex of S1 with ACE2 and the peptide. This is possible in the presence of another binding site for the S1 protein beside the receptor-binding domain for ACE2, which binds the peptide QAKTFLDKFNHEAEDLFYQ. Therefore, we conducted computational mapping of the S1 protein surface, revealing two additional binding sites located at some distance from the main receptor-binding domain on S1. We suggest the possibility to predict and test the short protein derived peptides for development of novel strategies in inhibiting virus infections. The online version contains supplementary material available at 10.1007/s10989-021-10324-7.

Category: Health

Type: Journal article

PubMed 34867130

DOI 10.1007/s10989-021-10324-7

Crossref 10.1007/s10989-021-10324-7

pii: 10324
pmc: PMC8634746


Publications 7.1.2