Structural studies and SH3 domain binding properties of a human antiviral salivary proline-rich peptide

Benedetta Righino, Davide Pirolli, Giorgia Radicioni, Valeria Marzano, Renato Longhi, Alessandro Arcovito, Maria Teresa Sanna, Maria Cristina De Rosa, Serena Paoluzi, Gianni Cesareni, Irene Messana, Massimo Castagnola, Alberto Vitali

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Pages (from-to)714-725
Number of pages12
JournalBiopolymers
DOIs
Publication statusPublished - Sep 1 2016
Externally publishedYes

Fingerprint

src Homology Domains
Proline
Peptides
Antiviral Agents
Bioactivity
Salivary Proline-Rich Proteins
Anti-HIV Agents
Signal transduction
Surface Plasmon Resonance
src-Family Kinases
Mouth Mucosa
Dichroism
Surface plasmon resonance
Fourier Transform Infrared Spectroscopy
Molecular Dynamics Simulation
Circular Dichroism
Saliva
Modulators
Molecular dynamics
Signal Transduction

Keywords

  • antiviral
  • circular dichroism
  • molecular modeling
  • proline-rich peptide
  • SH3 domain
  • Src kinases
  • surface plasmon resonance

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Biomaterials
  • Organic Chemistry

Cite this

Righino, B., Pirolli, D., Radicioni, G., Marzano, V., Longhi, R., Arcovito, A., ... Vitali, A. (2016). Structural studies and SH3 domain binding properties of a human antiviral salivary proline-rich peptide. Biopolymers, 714-725. https://doi.org/10.1002/bip.22889

Structural studies and SH3 domain binding properties of a human antiviral salivary proline-rich peptide. / Righino, Benedetta; Pirolli, Davide; Radicioni, Giorgia; Marzano, Valeria; Longhi, Renato; Arcovito, Alessandro; Sanna, Maria Teresa; De Rosa, Maria Cristina; Paoluzi, Serena; Cesareni, Gianni; Messana, Irene; Castagnola, Massimo; Vitali, Alberto.

In: Biopolymers, 01.09.2016, p. 714-725.

Research output: Contribution to journalArticle

Righino, B, Pirolli, D, Radicioni, G, Marzano, V, Longhi, R, Arcovito, A, Sanna, MT, De Rosa, MC, Paoluzi, S, Cesareni, G, Messana, I, Castagnola, M & Vitali, A 2016, 'Structural studies and SH3 domain binding properties of a human antiviral salivary proline-rich peptide', Biopolymers, pp. 714-725. https://doi.org/10.1002/bip.22889
Righino B, Pirolli D, Radicioni G, Marzano V, Longhi R, Arcovito A et al. Structural studies and SH3 domain binding properties of a human antiviral salivary proline-rich peptide. Biopolymers. 2016 Sep 1;714-725. https://doi.org/10.1002/bip.22889
Righino, Benedetta ; Pirolli, Davide ; Radicioni, Giorgia ; Marzano, Valeria ; Longhi, Renato ; Arcovito, Alessandro ; Sanna, Maria Teresa ; De Rosa, Maria Cristina ; Paoluzi, Serena ; Cesareni, Gianni ; Messana, Irene ; Castagnola, Massimo ; Vitali, Alberto. / Structural studies and SH3 domain binding properties of a human antiviral salivary proline-rich peptide. In: Biopolymers. 2016 ; pp. 714-725.
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