Structure Analysis of F1-ATPase via Molecular Dynamics

Abstract

F1-ATPase is comprised of five different subunits (α to e). The α3β3 hexamer contains nucleotide binding sites and γ rotates sequentially by a cooperative binding change mechanism for ATP synthesis and hydrolysis. The structures of β subunits, undergoing large conformational changes during the binding change mechanism, can be classified as tight (βDP), loose (βTP) or empty (βE). To elucidate the relationship between intrinsic dynamics of F1-ATPase and its function, we have carried out a equilibrium molecular dynamics simulation for a F1-ATPase crystal structure (PDB cord: 2JDI) for 30 ns. The structural features of each subunit and their inter-subunit interactions were analyzed by the residue fluctuations and correlation. Previous studies revealed that the catalytically active βDP subunit interacts strongly with αDP. However, we found that the non-catalytic pair, βDPαE also interacts strongly. This suggests that sandwiched βDP can efficiently transmit some structural change caused by the chemical reaction to the adjacent subunits. Furthermore, structural fluctuation of the γ subunit was correlated mainly with βDP. This result suggests that the chemical reaction on βDP can affect not only the conformational change for the other α, β subunits but also the γ-subunit rotation.