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

作者：Valery Celine; Deville Foillard Stephanie; Lefebvre Christelle; Taberner Nuria; Legrand Pierre; Meneau Florian; Meriadec Cristelle; Delvaux Camille; Bizien Thomas; Kasotakis Emmanouil; Lopez Iglesias Carmen; Gall Andrew; Bressanelli Stephane; Le Du Marie Helene; Paternostre Maite^*; Artzner Franck

来源：Nature Communications, 2015, 6(1): 7771.

DOI：10.1038/ncomms8771

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 beta-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.

• 出版日期2015-7
• 单位中国地震局