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Nat Commun. 2015 Jul 20;6:7771. doi: 10.1038/ncomms8771.

Atomic view of the histidine environment stabilizing higher-pH conformations of pH-dependent proteins.

Author information

1
1] Biomolecular Interaction Centre, School of Biological Sciences, University of Canterbury, 8140 Christchurch, New zealand [2] Ipsen, 5 Avenue du Canada, 91940 Les Ulis, France.
2
1] Ipsen, 5 Avenue du Canada, 91940 Les Ulis, France [2] CEA, Institute of Biology and Technologies of Saclay, 91191 CEA-Saclay, France [3] Institute for Integrative Biology of the Cell (I2BC), CEA, CNRS, Université Paris-Sud, 91191 CEA-Saclay, Gif sur Yvette, France.
3
CNRS, UMR 6251, Institut de Physique de Rennes, 263 av. Général Leclerc, Université Rennes I, 35042 Rennes Cedex, France.
4
Ipsen, 5 Avenue du Canada, 91940 Les Ulis, France.
5
Synchrotron SOLEIL, 91190 Gif sur Yvette, France.
6
1] CEA, Institute of Biology and Technologies of Saclay, 91191 CEA-Saclay, France [2] Institute for Integrative Biology of the Cell (I2BC), CEA, CNRS, Université Paris-Sud, 91191 CEA-Saclay, Gif sur Yvette, France.
7
Cryo-Electron Microscopy Unit. Scientific and Tecnological Centers of the University of Barcelona, E-08028 Barcelona, Spain.

Abstract

External stimuli are powerful tools that naturally control protein assemblies and functions. For example, during viral entry and exit changes in pH are known to trigger large protein conformational changes. However, the molecular features stabilizing the higher pH structures remain unclear. Here we elucidate the conformational change of a self-assembling peptide that forms either small or large nanotubes dependent on the pH. The sub-angstrom high-pH peptide structure reveals a globular conformation stabilized through a strong histidine-serine H-bond and a tight histidine-aromatic packing. Lowering the pH induces histidine protonation, disrupts these interactions and triggers a large change to an extended β-sheet-based conformation. Re-visiting available structures of proteins with pH-dependent conformations reveals both histidine-containing aromatic pockets and histidine-serine proximity as key motifs in higher pH structures. The mechanism discovered in this study may thus be generally used by pH-dependent proteins and opens new prospects in the field of nanomaterials.

PMID:
26190377
PMCID:
PMC4518280
DOI:
10.1038/ncomms8771
[Indexed for MEDLINE]
Free PMC Article

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