title: Atomic view of the histidine environment stabilizing higher-pH conformations of pH-dependent proteins.
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.
authors.affiliation: 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.
authors.forename: Céline
authors.initials: C
authors.lastname: Valéry
authors.affiliation: 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.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Deville-Foillard
authors.affiliation: CNRS, UMR 6251, Institut de Physique de Rennes, 263 av. Général Leclerc, Université Rennes I, 35042 Rennes Cedex, France.
authors.forename: Christelle
authors.initials: C
authors.lastname: Lefebvre
authors.affiliation: Ipsen, 5 Avenue du Canada, 91940 Les Ulis, France.
authors.forename: Nuria
authors.initials: N
authors.lastname: Taberner
authors.affiliation: Synchrotron SOLEIL, 91190 Gif sur Yvette, France.
authors.forename: Pierre
authors.identifier: 0000000324312255
authors.initials: P
authors.lastname: Legrand
authors.affiliation: Synchrotron SOLEIL, 91190 Gif sur Yvette, France.
authors.forename: Florian
authors.initials: F
authors.lastname: Meneau
authors.affiliation: CNRS, UMR 6251, Institut de Physique de Rennes, 263 av. Général Leclerc, Université Rennes I, 35042 Rennes Cedex, France.
authors.forename: Cristelle
authors.initials: C
authors.lastname: Meriadec
authors.affiliation: 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.
authors.forename: Camille
authors.initials: C
authors.lastname: Delvaux
authors.affiliation: CNRS, UMR 6251, Institut de Physique de Rennes, 263 av. Général Leclerc, Université Rennes I, 35042 Rennes Cedex, France.
authors.forename: Thomas
authors.initials: T
authors.lastname: Bizien
authors.affiliation: 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.
authors.forename: Emmanouil
authors.initials: E
authors.lastname: Kasotakis
authors.affiliation: Cryo-Electron Microscopy Unit. Scientific and Tecnological Centers of the University of Barcelona, E-08028 Barcelona, Spain.
authors.forename: Carmen
authors.initials: C
authors.lastname: Lopez-Iglesias
authors.affiliation: 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.
authors.forename: Andrew
authors.initials: A
authors.lastname: Gall
authors.affiliation: 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.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Bressanelli
authors.affiliation: 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.
authors.forename: Marie-Hélène
authors.initials: MH
authors.lastname: Le Du
authors.affiliation: 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.
authors.forename: Maïté
authors.initials: M
authors.lastname: Paternostre
authors.affiliation: CNRS, UMR 6251, Institut de Physique de Rennes, 263 av. Général Leclerc, Université Rennes I, 35042 Rennes Cedex, France.
authors.forename: Franck
authors.initials: F
authors.lastname: Artzner
mesh_terms: D018360:Crystallography, X-Ray; D006639:Histidine / Q000737:chemistry / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D008958:Models, Molecular; D045333:Nanotubes, Peptide / Q000737:chemistry; D061848:Optical Imaging; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D017550:Spectroscopy, Fourier Transform Infrared; D013059:Spectrum Analysis, Raman; D017329:Triptorelin Pamoate / Q000737:chemistry / Q000378:metabolism*
chemical_list: D045333:Nanotubes, Peptide; D017329:Triptorelin Pamoate; D006639:Histidine