TY - JOUR
T1 - pH-dependent conformational switch activates the inhibitor of transcription elongation
AU - Laptenko, Oleg
AU - Kim, Seung Sup
AU - Lee, Jookyung
AU - Starodubtseva, Marina
AU - Cava, Fellipe
AU - Berenguer, Jose
AU - Kong, Xiang Peng
AU - Borukhov, Sergei
N1 - Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.
PY - 2006/5/17
Y1 - 2006/5/17
N2 - Gfh1, a transcription factor from Thermus thermophilus, inhibits all catalytic activities of RNA polymerase (RNAP). We characterized the Gfh1 structure, function and possible mechanism of action and regulation. Gfh1 inhibits RNAP by competing with NTPs for coordinating the active site Mg 2+ ion. This coordination requires at least two aspartates at the tip of the Gfh1 N-terminal coiled-coil domain (NTD). The overall structure of Gfh1 is similar to that of the Escherichia coli transcript cleavage factor GreA, except for the flipped orientation of the C-terminal domain (CTD). We show that depending on pH, Gfh1-CTD exists in two alternative orientations. At pH above 7, it assumes an inactive 'flipped' orientation seen in the structure, which prevents Gfh1 from binding to RNAP. At lower pH, Gfh1-CTD switches to an active 'Gre-like' orientation, which enables Gfh1 to bind to and inhibit RNAP.
AB - Gfh1, a transcription factor from Thermus thermophilus, inhibits all catalytic activities of RNA polymerase (RNAP). We characterized the Gfh1 structure, function and possible mechanism of action and regulation. Gfh1 inhibits RNAP by competing with NTPs for coordinating the active site Mg 2+ ion. This coordination requires at least two aspartates at the tip of the Gfh1 N-terminal coiled-coil domain (NTD). The overall structure of Gfh1 is similar to that of the Escherichia coli transcript cleavage factor GreA, except for the flipped orientation of the C-terminal domain (CTD). We show that depending on pH, Gfh1-CTD exists in two alternative orientations. At pH above 7, it assumes an inactive 'flipped' orientation seen in the structure, which prevents Gfh1 from binding to RNAP. At lower pH, Gfh1-CTD switches to an active 'Gre-like' orientation, which enables Gfh1 to bind to and inhibit RNAP.
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U2 - 10.1038/sj.emboj.7601094
DO - 10.1038/sj.emboj.7601094
M3 - Article
C2 - 16628221
AN - SCOPUS:33646773242
VL - 25
SP - 2131
EP - 2141
JO - EMBO Journal
JF - EMBO Journal
SN - 0261-4189
IS - 10
ER -