title: Conformational states of HAMP domains interacting with sensory rhodopsin membrane systems: an integrated all-atom and coarse-grained molecular dynamics simulation approach.
abstract: Understanding the downstream signaling mechanism of sensory rhodopsin and its cognate transducer complex (srII-htrII) has long been a challenge in the field of photoreceptor research. Here, an integration of all-atom and coarse-grained (CG) molecular dynamics (MD) simulations in different srII-htrII complex states is carried out. It is shown that the cytoplasmic four-helix HAMP dimer gives rise to a gear-box model interaction with discrete hydrophobic packing in Natronomonas pharaonis (Np). Structural analysis in all-atom and CG-MD reveals a stable conformational state in the physiological environment (323 K and 1.15 M salt). Comparative analysis in the ground and intermediate state conformations reveals substantial inter-HAMP interactions in the intermediate state with uniform clockwise (+10° to +30°) and counterclockwise (-20° to -40°) rotations in the α1 helix and the α2 helix of the monomer, respectively. Low temperature and low salt environments (283 K and 0.15 M) significantly affect srII-htrII binding affinity in both states with unusual helix bending. The distinguished control cable, knob-into-holes packing and piston-like movements in HAMP helices are found in the intermediate state complex. The N-terminal htrII (159 residues) coupled with srII yields a binding energy (ΔGbind) of -309.22, -436.53 and -331.11 kJ mol-1in the MM/PBSA calculation for the NphtrII homodimer, the NpsrII-htrII ground state conformation and the NpsrII-htrII intermediate state conformation, respectively. Only the HAMP1 domain shows a very low ΔGbindvalue (-21.03 kJ mol-1) for the ground state in comparison to that for the intermediate state (-54.68 kJ mol-1). The structural analysis highlights the key residues that include Y199srII, T189srII, E43htrII, T86htrII, M100htrII, E116htrII, E126htrIIand S130htrIIfor complex stabilization and signal transduction.
authors.affiliation: Laboratory of Molecular Biophysics, Institute for Protein Research, Osaka University, 5650871, Japan. tfjwr@protein.osaka-u.ac.jp.
authors.forename: Bikash Ranjan
authors.initials: BR
authors.lastname: Sahoo
authors.affiliation: Laboratory of Molecular Biophysics, Institute for Protein Research, Osaka University, 5650871, Japan. tfjwr@protein.osaka-u.ac.jp.
authors.forename: Toshimichi
authors.initials: T
authors.lastname: Fujiwara
mesh_terms: D000595:Amino Acid Sequence; D057927:Hydrophobic and Hydrophilic Interactions; D056004:Molecular Dynamics Simulation; D009154:Mutation; D019906:Nuclear Magnetic Resonance, Biomolecular; D011487:Protein Conformation; D054730:Protein Interaction Domains and Motifs; D055503:Protein Multimerization; D025603:Sensory Rhodopsins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D013816:Thermodynamics
chemical_list: D025603:Sensory Rhodopsins