Energetic and structural details of the trigger-loop closing transition in RNA polymerase II.
An evolutionarily conserved element in RNA polymerase II, the trigger loop (TL), has been suggested to play an important role in the elongation rate, fidelity of selection of the matched nucleoside triphosphate (NTP), catalysis of transcription elongation, and translocation in both eukaryotes and prokaryotes. In response to NTP binding, the TL undergoes large conformational changes to switch between distinct open and closed states to tighten the active site and avail catalysis. A computational strategy for characterizing the conformational transition pathway is presented to bridge the open and closed states of the TL. Information from a large number of independent all-atom molecular dynamics trajectories from Hamiltonian replica exchange and targeted molecular dynamics simulations is gathered together to assemble a connectivity map of the conformational transition. The results show that with a cognate NTP, TL closing should be a spontaneous process. One major intermediate state is identified along the conformational transition pathway, and the key structural features are characterized. The complete pathway from the open TL to the closed TL provides a clear picture of the TL closing.
Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing, USA.
Beibei
B
Wang
Alexander V
AV
Predeus
Zachary F
ZF
Burton
Michael
M
Feig
D000595:Amino Acid Sequence; D001665:Binding Sites; D003854:Deoxyribonucleotides / Q000737:chemistry / Q000378:metabolism; D056004:Molecular Dynamics Simulation; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary; D012319:RNA Polymerase II / Q000737:chemistry* / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry* / Q000378:metabolism
D003854:Deoxyribonucleotides; D029701:Saccharomyces cerevisiae Proteins; D012319:RNA Polymerase II; C511736:RPB1 protein, S cerevisiae