The Streptomyces master regulator BldD binds c-di-GMP sequentially to create a functional BldD2-(c-di-GMP)4 complex. Issue 11 (26th April 2017)

• Record Type: Journal Article
• Authors: Schumacher, Maria A.; Zeng, Wenjie; Findlay, Kim C.; Buttner, Mark J.; Brennan, Richard G.; Tschowri, Natalia
• Is Part Of: Nucleic acids research. Volume 45:Issue 11(2017)
• Page Start: 6923
• Page End: 6933
• Publication Date: 2017-04-26
• Subjects: Nucleic acids -- Periodicals; Molecular biology -- Periodicals; 572.805
• DOI: 10.1093/nar/gkx287
• Languages: English
• ISSNs: 0305-1048

Abstract

Abstract: Streptomyces are ubiquitous soil bacteria that undergo a complex developmental transition coinciding with their production of antibiotics. This transition is controlled by binding of a novel tetrameric form of the second messenger, 3΄-5΄ cyclic diguanylic acid (c-di-GMP) to the master repressor, BldD. In all domains of life, nucleotide-based second messengers allow a rapid integration of external and internal signals into regulatory pathways that control cellular responses to changing conditions. c-di-GMP can assume alternative oligomeric states to effect different functions, binding to effector proteins as monomers, intercalated dimers or, uniquely in the case of BldD, as a tetramer. However, at physiological concentrations c-di-GMP is a monomer and little is known about how higher oligomeric complexes assemble on effector proteins and if intermediates in assembly pathways have regulatory significance. Here, we show that c-di-GMP binds BldD using an ordered, sequential mechanism and that BldD function necessitates the assembly of the BldD2 -(c-di-GMP)4 complex.