[Molecular Dynamics of N- and C-terminal Interactions during Autoinhibition and Activation of Formin mDial].
With the method of molecular dynamics, pairs of amino acid residues have been identified on the surface of the interacting formin mDial domains: DID-DAD, which are responsible for the autoinhibition of formin, and the GTPase Rho-DID domain, and control activation. It was found that the most stable interactions are ionic interactions between Glu178 residue and Arg248 residue, as well as hydrophobic interactions between Thr175 and Phe247. The strongest interactions proved to be between the DID domain with Rho-GTPase. These interactions are mediated by specific triple ionic interactions between positively charged amino acid in Rho, and a triplet of amino acids in DID, consisting of two negatively charged amino acids, separated by one uncharged. Binding sites for Rho-GTPase and DAD partially overlap, but various amino acids on the DID participate in interactions with different domains. We discuss the possible conformational changes in formin domains during activation and inactivation.
I A
IA
Orshanskiy
A V
AV
Popinako
O I
OI
Volokh
K V
KV
Shaitan
O S
OS
Sokolova
D000818:Animals; D001120:Arginine / Q000737:chemistry; D001665:Binding Sites; D002352:Carrier Proteins / Q000737:chemistry*; D000080865:Formins; D018698:Glutamic Acid / Q000737:chemistry; D057927:Hydrophobic and Hydrophilic Interactions; D051379:Mice; D056004:Molecular Dynamics Simulation; D009994:Osmolar Concentration; D010649:Phenylalanine / Q000737:chemistry; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D017433:Protein Structure, Secondary; D055672:Static Electricity; D013912:Threonine / Q000737:chemistry; D020741:rho GTP-Binding Proteins / Q000737:chemistry*
D002352:Carrier Proteins; C491464:Diap1 protein, mouse; D000080865:Formins; D013912:Threonine; D018698:Glutamic Acid; D010649:Phenylalanine; D001120:Arginine; D020741:rho GTP-Binding Proteins