Role of histidine for charge regulation of unstructured peptides at interfaces and in bulk.

Summary, in English

Histidine rich, unstructured peptides adsorb to charged interfaces such as mineral surfaces and microbial cell membranes. At a molecular level, we investigate the adsorption mechanism as a function of pH, salt, and multivalent ions showing that (1) proton charge fluctuations are - in contrast to the majority of proteins - optimal at neutral pH, promoting electrostatic interactions with anionic surfaces through charge regulation, and (2) specific zinc(II)-histidine binding competes with protons and ensures an unusually constant charge distribution over a broad pH interval. In turn this further enhances surface adsorption. Our analysis is based on atomistic molecular dynamics simulations, coarse grained Metropolis Monte Carlo, and classical polymer density functional theory. This multi-scale modelling provides a consistent picture in good agreement with experimental data on Histatin 5, an antimicrobial salivary peptide. Biological function is discussed and we suggest that charge regulation is a significant driving force for the remarkably robust activity of histidine rich antimicrobial peptides.

• Author: Anil Kurut Sabanoglu; Joao Henriques; Jan Forsman; Marie Skepö; Mikael Lund
• Department/s: Computational Chemistry; eSSENCE: The e-Science Collaboration
• Publishing year: 2014
• Language: English
• Pages: 657-667
• Publication/Series: Proteins
• Volume: 82
• Issue: 4
• Full text: - 2 MB; Download statistics
• Links: http://dx.doi.org/10.1002/prot.24445
• Document type: Journal article
• Publisher: John Wiley & Sons Inc.
• Topic: Theoretical Chemistry (including Computational Chemistry)
• Status: Published
• ISBN/ISSN/Other: ISSN: 0887-3585