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 language | English |
|---|---|
| Pages (from-to) | 714-725 |
| Number of pages | 12 |
| Journal | Biopolymers |
| DOIs | |
| Publication status | Published - Sep 1 2016 |
| Externally published | Yes |
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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
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 journal › Article
}
TY - JOUR
T1 - Structural studies and SH3 domain binding properties of a human antiviral salivary proline-rich peptide
AU - Righino, Benedetta
AU - Pirolli, Davide
AU - Radicioni, Giorgia
AU - Marzano, Valeria
AU - Longhi, Renato
AU - Arcovito, Alessandro
AU - Sanna, Maria Teresa
AU - De Rosa, Maria Cristina
AU - Paoluzi, Serena
AU - Cesareni, Gianni
AU - Messana, Irene
AU - Castagnola, Massimo
AU - Vitali, Alberto
PY - 2016/9/1
Y1 - 2016/9/1
N2 - 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.
AB - 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.
KW - antiviral
KW - circular dichroism
KW - molecular modeling
KW - proline-rich peptide
KW - SH3 domain
KW - Src kinases
KW - surface plasmon resonance
UR - http://www.scopus.com/inward/record.url?scp=84988667537&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84988667537&partnerID=8YFLogxK
U2 - 10.1002/bip.22889
DO - 10.1002/bip.22889
M3 - Article
C2 - 27272460
AN - SCOPUS:84988667537
SP - 714
EP - 725
JO - Biopolymers
JF - Biopolymers
SN - 0006-3525
ER -