The trans-activation domain of the sporulation response regulator Spo0A revealed by X-ray crystallography

Citation
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
Citations number
57
Categorie Soggetti
Microbiology
Journal title
MOLECULAR MICROBIOLOGY
ISSN journal
0950382X → ACNP
Volume
38
Issue
2
Year of publication
2000
Pages
198 - 212
Database
ISI
SICI code
0950-382X(200010)38:2<198:TTDOTS>2.0.ZU;2-C
Abstract
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.