Structural studies and SH3 domain binding properties of a human antiviral salivary proline-rich peptide.
Human saliva contains hundreds of small proline-rich peptides originated by the proteolytic cleavage of the salivary basic Proline-Rich Proteins. Nevertheless only for few of them a specific biological activity has been assigned to date. Among them, the 1932 Da peptide (p1932) has been patented as an anti-HIV agent. In order to shed light on the possible mechanism of action of this peptide, we assessed in this study, by means of molecular dynamics calculations, circular dichroism and FTIR spectroscopic techniques, that p1932 has an intrinsic propensity to adopt a polyproline-II helix arrangement. This structural feature combined with the presence of PxxP motifs in its primary structure, represents an essential property for the exploitation of several biological activities. Next to these findings, we recently demonstrated the ability of this peptide to be internalized within cells of the oral mucosa, thus we focused onto a possible intracellular target, represented by the SH3 domains family. Its ability to interact with selected SH3 domains was finally assayed by Surface Plasmon Resonance spectroscopy. As a result, only Fyn, Hck, and c-Src SH3 domains gave positive results in terms of interaction, showing dissociation constants ranging from nanomolar to micromolar values having the best performer a KD of 148 nM. It is noteworthy that all the interacting domains belong to the Src kinases family, suggesting a role for p1932 as a modulator of the signal transduction pathways mediated by these kinases. © 2016 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 106: 714-725, 2016.
Istituto di Biochimica e Biochimica Clinica, Facoltà di Medicina, Università Cattolica, L.Go F. Vito, 1, Rome, 00168, Italy.
Benedetta
B
Righino
Istituto di Biochimica e Biochimica Clinica, Facoltà di Medicina, Università Cattolica, L.Go F. Vito, 1, Rome, 00168, Italy.
Davide
D
Pirolli
Istituto di Biochimica e Biochimica Clinica, Facoltà di Medicina, Università Cattolica, L.Go F. Vito, 1, Rome, 00168, Italy.
Giorgia
G
Radicioni
Istituto di Biochimica e Biochimica Clinica, Facoltà di Medicina, Università Cattolica, L.Go F. Vito, 1, Rome, 00168, Italy.
Valeria
V
Marzano
Istituto di Chimica del Riconoscimento Molecolare, C.N.R, via Mario Bianco, 9, Milan, 20100, Italy.
Renato
R
Longhi
Istituto di Biochimica e Biochimica Clinica, Facoltà di Medicina, Università Cattolica, L.Go F. Vito, 1, Rome, 00168, Italy.
Alessandro
A
Arcovito
Dipartimento di Scienze della Vita e dell'Ambiente, Monserrato, 09042, Italy, Università di Cagliari, Cittadella Universitaria, Cagliari.
Maria Teresa
MT
Sanna
Istituto di Chimica di Riconoscimento Molecolare, C.N.R. Rome, L.Go F. Vito, 1, Rome, 00168, Italy.
Maria Cristina
MC
De Rosa
Dipartimento di Biologia, Università di Tor Vergata, Rome, 00173, Italy.
Serena
S
Paoluzi
Dipartimento di Biologia, Università di Tor Vergata, Rome, 00173, Italy.
Gianni
G
Cesareni
Dipartimento di Scienze della Vita e dell'Ambiente, Monserrato, 09042, Italy, Università di Cagliari, Cittadella Universitaria, Cagliari.
Irene
I
Messana
Istituto di Biochimica e Biochimica Clinica, Facoltà di Medicina, Università Cattolica, L.Go F. Vito, 1, Rome, 00168, Italy.|Istituto di Chimica di Riconoscimento Molecolare, C.N.R. Rome, L.Go F. Vito, 1, Rome, 00168, Italy.
Massimo
M
Castagnola
Istituto di Chimica di Riconoscimento Molecolare, C.N.R. Rome, L.Go F. Vito, 1, Rome, 00168, Italy. alberto.vitali@icrm.cnr.it.
Alberto
A
Vitali
D019380:Anti-HIV Agents / Q000737:chemistry*; D023181:Antimicrobial Cationic Peptides / Q000737:chemistry*; D006801:Humans; D056004:Molecular Dynamics Simulation; D055273:Salivary Proline-Rich Proteins / Q000737:chemistry*; D020349:Surface Plasmon Resonance; D018909:src Homology Domains
D019380:Anti-HIV Agents; D023181:Antimicrobial Cationic Peptides; D055273:Salivary Proline-Rich Proteins; C072212:PR 39
SH3 domain; Src kinases; antiviral; circular dichroism; molecular modeling; proline-rich peptide; surface plasmon resonance