Two Distinct States of the HAMP Domain From Sensory Rhodopsin Transducer Observed in Unbiased Molecular Dynamics Simulations

PLoS One. 2013 Jul 2;8(7):e66917. doi: 10.1371/journal.pone.0066917. Print 2013.

Abstract

HAMP domain is a ubiquitous module of bacterial and archaeal two-component signaling systems. Considerable progress has been made recently in studies of its structure and conformational changes. However, the mechanism of signal transduction through the HAMP domain is not clear. It remains a question whether all the HAMPs have the same mechanism of action and what are the differences between the domains from different protein families. Here, we present the results of unbiased molecular dynamics simulations of the HAMP domain from the archaeal phototaxis signal transducer NpHtrII. Two distinct conformational states of the HAMP domain are observed, that differ in relative position of the helices AS1 and AS2. The longitudinal shift is roughly equal to a half of an α-helix turn, although sometimes it reaches one full turn. The states are closely related to the position of bulky hydrophobic aminoacids at the HAMP domain core. The observed features are in good agreement with recent experimental results and allow us to propose that the states detected in the simulations are the resting state and the signaling state of the NpHtrII HAMP domain. To the best of our knowledge, this is the first observation of the same HAMP domain in different conformations. The simulations also underline the difference between AMBER ff99-SB-ILDN and CHARMM22-CMAP forcefields, as the former favors the resting state and the latter favors the signaling state.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Archaeal Proteins / chemistry*
  • Halobacteriaceae / chemistry*
  • Hydrophobic and Hydrophilic Interactions
  • Molecular Dynamics Simulation*
  • Protein Structure, Secondary
  • Protein Structure, Tertiary
  • Sensory Rhodopsins / chemistry*
  • Signal Transduction

Substances

  • Archaeal Proteins
  • HtrII protein, Natronobacterium pharaonis
  • Sensory Rhodopsins

Grant support

The simulations were performed with a grant for computing time at the Juelich Supercomputing Center. The work was supported by the program “Chaires d’excellence” edition 2008 of ANR France, CEA(IBS) – HGF(FZJ) STC 5.1 specific agreement, the MC grant (Marie Curie, FP7-PEOPLE-2007-1-1-ITN, project SBMPs) and an EC FP7 grant for the EDICT consortium (HEALTH-201924). Part of this work was supported by BMBF (PhoNa – Photonic Nanomaterials). The work was partially supported by the Federal Target Program «Scientific and academic research cadres of innovative Russia for 2009–2013 years and by the “Molecular and Cellular Biology” program of the Russian Academy of Sciences. The authors greatly acknowledge support of this work by ONEXIM, Russia. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.