The 2.5 angstrom resolution x-ray crystal structure of the Escherichia
coil RNA polymerase (RNAP) alpha subunit amino-terminal domain (alpha
NTD), which is necessary and sufficient to dimerize and assemble the
other RNAP subunits into a transcriptionally active enzyme and contain
s all of the sequence elements conserved among eukaryotic alpha homolo
gs, has been determined. The alpha NTD monomer comprises two distinct,
flexibly linked domains, only one of which participates in the dimer
interface. In the alpha NTD dimer, a pair of helices from one monomer
interact with the cognate helices of the other to form an extensive hy
drophobic core. ALL of the determinants for interactions with the othe
r RNAP subunits lie on one face of the aNTD dimer. Sequence alignments
, combined with secondary-structure predictions, support proposals tha
t a heterodimer of the eukaryotic RNAP subunits related to Saccharomyc
es cerevisiae Rpb3 and Rpb11 plays the role of the alpha NTD dimer in
prokaryotic RNAP.