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

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. © 2016 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 106: 714-725, 2016.

The Post-Translational Modifications of Human Salivary Peptides and Proteins Evidenced by Top-Down Platforms

“…The intrinsic propensity of some fragments to adopt a polyproline-II helix arrangement joined to PXXP motifs was suggestive of the interaction with the SH3 domain family [ 33 ]. Interestingly, interactions were highlighted with Fyn, Hck, and c-Src SH3 domains [ 34 ], which are included in the Src kinases family, suggesting that some basic bPRPs can be involved in the signal transduction pathways modulated by these kinases. Only a small amount of data on correlations between genes of bPRPs and diseases linked to their allelic variants has been reported so far.…”

Customized Therapeutic Surface Coatings for Dental Implants

“…Human beta defensins peptides have an immuno-modulatory effect that promotes bone remodeling [267]. Similarly, Righino et al reported the new approach for mimicking human antiviral salivary proline-rich peptide (PRP) for medical purposes [277]. Warnke et al reported a recombinant human beta defensin-2 coating for biocompatibility assessment with the human mesenchymal stem cells (hMSCs) and human osteoblasts, and found no toxicity [278].…”

Cryptides: latent peptides everywhere

“…Surface plasmon resonance spectroscopy evidenced specific interactions only with Fyn, Hck, and c-Src SH3 domains at nanomolar to micromolar values of dissociation constants. Interestingly, these interacting domains are all included in the Src kinases family, suggesting that p1932 can be involved in the signal transduction pathways modulated by these kinases (Righino et al 2016). From Table 2, it is evident that p1932 is one of a large series of putative salivary cryptides waiting for a more detailed study of their functions.…”