Mechanism of Deep-Sea Fish α-Actin Pressure Tolerance Investigated by Molecular Dynamics Simulations

<div><p>The pressure tolerance of monomeric α-actin proteins from the deep-sea fish <i>Coryphaenoides armatus</i> and <i>C. yaquinae</i> was compared to that of non-deep-sea fish <i>C. acrolepis</i>, carp, and rabbit/human/chicken actins using molecular dynamics simulations at 0.1 and 60 MPa. The amino acid sequences of actins are highly conserved across a variety of species. The actins from <i>C. armatus</i> and <i>C. yaquinae</i> have the specific substitutions Q137K/V54A and Q137K/L67P, respectively, relative to <i>C. acrolepis</i>, and are pressure tolerant to depths of at least 6000 m. At high pressure, we observed significant changes in the salt bridge patterns in deep-sea fish actins, and these changes are expected to stabilize ATP binding and subdomain arrangement. Salt bridges between ATP and K137, formed in deep-sea fish actins, are expected to stabilize ATP binding even at high pressure. At high pressure, deep-sea fish actins also formed a greater total number of salt bridges than non-deep-sea fish actins owing to the formation of inter-helix/strand and inter-subdomain salt bridges. Free energy analysis suggests that deep-sea fish actins are stabilized to a greater degree by the conformational energy decrease associated with pressure effect.</p>