Rj. Lewis et al., The trans-activation domain of the sporulation response regulator Spo0A revealed by X-ray crystallography, MOL MICROB, 38(2), 2000, pp. 198-212
Sporulation in Bacillus involves the induction of scores of genes in a temp
orally and spatially co-ordinated programme of cell development. Its initia
tion is under the control of an expanded two-component signal transduction
system termed a phosphorelay. The master control element in the decision to
sporulate is the response regulator, Spo0A, which comprises a receiver or
phosphoacceptor domain and an effector or transcription activation domain.
The receiver domain of Spo0A shares sequence similarity with numerous respo
nse regulators, and its structure has been determined in phosphorylated and
unphosphorylated forms. However, the effector domain (C-Spo0A) has no dete
ctable sequence similarity to any other protein, and this lack of structura
l information is an obstacle to understanding how DNA binding and transcrip
tion activation are controlled by phosphorylation in Spo0A. Here, we report
the crystal structure of C-Spo0A from Bacillus stearothermophilus revealin
g a single alpha -helical domain comprising six alpha -helices in an unprec
edented fold. The structure contains a helix-turn-helix as part of a three
alpha -helical bundle reminiscent of the catabolite gene activator protein
(CAP), suggesting a mechanism for DNA binding. The residues implicated in f
orming the sigma (A)-activating region clearly cluster in a flexible segmen
t of the polypeptide on the opposite side of the structure from that predic
ted to interact with DNA. The structural results are discussed in the conte
xt of the rich array of existing mutational data.