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

Kurut Sabanoglu, Anil LU ; Henriques, Joao LU ; Forsman, Jan LU ; Skepö, Marie LU and Lund, Mikael LU (2014) In Proteins 82(4). p.657-667
Abstract
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... (More)
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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Proteins
volume
82
issue
4
pages
657 - 667
publisher
John Wiley & Sons
external identifiers
  • pmid:24123297
  • wos:000332306500013
  • scopus:84895546964
ISSN
0887-3585
DOI
10.1002/prot.24445
language
English
LU publication?
yes
id
af0bc723-ecbe-47cf-a77a-7d940a7e521d (old id 4143298)
date added to LUP
2013-11-12 17:18:20
date last changed
2017-07-30 03:25:10
@article{af0bc723-ecbe-47cf-a77a-7d940a7e521d,
  abstract     = {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       = {Kurut Sabanoglu, Anil and Henriques, Joao and Forsman, Jan and Skepö, Marie and Lund, Mikael},
  issn         = {0887-3585},
  language     = {eng},
  number       = {4},
  pages        = {657--667},
  publisher    = {John Wiley & Sons},
  series       = {Proteins},
  title        = {Role of histidine for charge regulation of unstructured peptides at interfaces and in bulk.},
  url          = {http://dx.doi.org/10.1002/prot.24445},
  volume       = {82},
  year         = {2014},
}