Model of a T7 RNAP transcription complex. The structures shown are
based on the experimentally determined structure of the T7 RNAP
initiation complex (6). In the polymerase, the N-terminal domain is
tan, the thumb domain is green, the intercalating hairpin that directs
the template strand into the active site (residues 230–250) is pink,
the N-terminal surface-exposed binding site for exogenous RNA (21) is
brown, the specificity loop () is dark blue, and the 7-aa
interval to which the −9 crosslink is made (744) is yellow. A
putative 8-bp RNA⋅DNA hybrid has been modeled into the DNA binding
cleft by homology modeling to the TaqI DNA polymerase
primer/template complex (20) by superimposing D537, D812, and Y639 in
T7 RNAP (PDB ID QLN), with the corresponding residues in
TaqI DNAP (PDB ID TAU) using weblab
viewerpro 3.5 (Molecular Simulations, Waltham,
MA). The template strand is green, the non-template strand cyan, and
the newly made RNA red. In this view, the promoter is to the right, the
active site is at the left end of the RNA⋅DNA hybrid, and the
front of the cleft obscures the active site and much of the template
strand of the RNA⋅DNA hybrid. Arrows show the suggested exit
pathways for the nascent transcript as proposed by Cheetham and Steitz
(6) or in this work (arrows I and II, respectively). To the right of
the overall complex are shown close-up views of the specificity loop,
the RNA⋅DNA hybrid, and the binding region of the promoter from
two different perspectives. The complex has been rotated such that the
view is now under the specificity loop and the template strand of the
RNA⋅DNA hybrid is now visible. The first two nucleotides of the
nascent RNA are shown in wireframe, and the alpha carbons of the two
Asp residues that define the active site (D537, D812) are shown as
black spheres. The RNA has been extended by 1 nt (black) to show the
proximity of the modeled base at −9 to the specificity loop. In this
model, 2–3 nt of unpaired template strand would be required to transit
the specificity loop and reestablish duplex DNA at the upstream border
of the transcription bubble.