TY - JOUR
T1 - Atomic view of the histidine environment stabilizing higher-pH conformations of pH-dependent proteins
AU - Valery, Celine
AU - Deville-Foillard, Stephanie
AU - Lefebvre, Christelle
AU - Taberner, Nuria
AU - Legrand, Pierre
AU - Meneau, Florian
AU - Meriadec, Cristelle
AU - Delvaux, Camille
AU - Bizien, Thomas
AU - Kasotakis, Emmanouil
AU - Lopez-Iglesias, Carmen
AU - Gall, Andrew
AU - Bressanelli, Stephane
AU - Le Du, Marie-Helene
AU - Paternostre, Maite
AU - Artzner, Franck
PY - 2015/7
Y1 - 2015/7
N2 - 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 ?-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.
AB - 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 ?-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.
U2 - 10.1038/ncomms8771
DO - 10.1038/ncomms8771
M3 - Article
SN - 2041-1723
VL - 6
JO - Nature Communications
JF - Nature Communications
M1 - 7771
ER -