The mouth is the first portion of the alimentary canal, it functions in the initial stage of food digestion. Saliva is found in the mouth where it serves several purposes including in the initiating the preliminary stages of digestion, maintaining the mineral phases of teeth, and protecting against antigens. Consequently, saliva is a complex biological fluid that contains both proteins and ions which are required to regulate these processes. Histatin 5 is a histidine rich antimicrobial protein found in saliva, and one of the first lines of defence in the innate immune system. Histatin 5 has been widely classified as an intrinsically disordered protein (IDP), which means that it maintains its function without adopting a folded conformation. IDPs are known to form functional oligomers and in some cases, insoluble disease related aggregates. It is therefore vital to understand processes and mechanisms that control pathway distribution. The exact mechanism through which Histatin 5 performs it antimicrobial function is not yet precisely understood. We show that Histatin 5 can interact with membrane mimetics and that this interaction is promoted by the presence of the zinc divalent cation. Divalent cations found in saliva, including Zn<sup>2+</sup>, can initiate IDP oligomerisation through the interaction with histidine residues. W apply a multi-disciplinary approach, using small angle X-ray scattering, nuclear magnetic resonance spectroscopy, calorimetry, and Monte Carlo simulations to show that that Histatin 5, forms highly dynamic oligomers in the presence of Zn(II). The process is critically dependent upon interaction between Zn(II) ions, and distinct histidine rich binding motifs, which allows for thermodynamic switching between the states. We propose that the interaction between zinc and histidine residues may be important for membrane interactions and the consequent antimicrobial activity of Histatin 5.

Dynamical oligomerisation of histidine rich intrinsically disordered proteins is regulated through zinc-histidine interactions

Macromolecular Chemistry: The Second Century

[Author Benefits](https://scimeetings.acs.org/?utm_source=pubs_content_marketing&utm_medium=website&utm_campaign=0320_MCF_NPI_Launch_Spring_Homepage&ref=pubs_content_marketing)

[How to use SciMeetings](https://storage.googleapis.com/dl.morressier.com/acs/SciMeetings-ACSSpring2020-HowToGuide_M3020-Final.pdf)

[Frequently Asked Questions](https://storage.googleapis.com/dl.morressier.com/acs/SciMtng_ACSNMSp2020_FAQ_M3120_Final.pdf)

ACS Spring 2020 National Meeting & Expo

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.