Pivotal Roles for the Receiver Domain in the Mechanism of Action of the Response Regulator RamR of Streptomyces coelicolor

2005 ◽  
Vol 351 (5) ◽  
pp. 1030-1047 ◽  
Author(s):  
Tamara J. O'Connor ◽  
Justin R. Nodwell
Keyword(s):  
Mechanism Of Action ◽  
Response Regulator ◽  
Streptomyces Coelicolor ◽  
Receiver Domain

scholarly journals Structures of full-length VanR from Streptomyces coelicolor in both the inactive and activated states

2021 ◽  
Vol 77 (8) ◽  
Author(s):  
Lina J. Maciunas ◽  
Nadia Porter ◽  
Paula J. Lee ◽  
Kushol Gupta ◽  
Patrick J. Loll
Keyword(s):  
Resistance Genes ◽  
Bacterial Infections ◽  
Analytical Ultracentrifugation ◽  
Response Regulator ◽  
Streptomyces Coelicolor ◽  
Full Length ◽  
Phosphoryl Group ◽  
Two Component System ◽  
Receiver Domain ◽  
Serious Bacterial Infections

Vancomycin has historically been used as a last-resort treatment for serious bacterial infections. However, vancomycin resistance has become widespread in certain pathogens, presenting a serious threat to public health. Resistance to vancomycin is conferred by a suite of resistance genes, the expression of which is controlled by the VanR–VanS two-component system. VanR is the response regulator in this system; in the presence of vancomycin, VanR accepts a phosphoryl group from VanS, thereby activating VanR as a transcription factor and inducing expression of the resistance genes. This paper presents the X-ray crystal structures of full-length VanR from Streptomyces coelicolor in both the inactive and activated states at resolutions of 2.3 and 2.0 Å, respectively. Comparison of the two structures illustrates that phosphorylation of VanR is accompanied by a disorder-to-order transition of helix 4, which lies within the receiver domain of the protein. This transition generates an interface that promotes dimerization of the receiver domain; dimerization in solution was verified using analytical ultracentrifugation. The inactive conformation of the protein does not appear intrinsically unable to bind DNA; rather, it is proposed that in the activated form DNA binding is enhanced by an avidity effect contributed by the receiver-domain dimerization.

scholarly journals Crystal structure of nonphosphorylated receiver domain of the stress response regulator RcsB fromEscherichia coli

2016 ◽  
Vol 25 (12) ◽  
pp. 2216-2224 ◽  
Author(s):  
Ekaterina V. Filippova ◽  
Zdzislaw Wawrzak ◽  
Jiapeng Ruan ◽  
Sergii Pshenychnyi ◽  
Richard M. Schultz ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Stress Response ◽  
Response Regulator ◽  
Fromescherichia Coli ◽  
Receiver Domain

scholarly journals Deciphering the activation and recognition mechanisms of Staphylococcus aureus response regulator ArlR

2019 ◽  
Vol 47 (21) ◽  
pp. 11418-11429 ◽  
Author(s):  
Zhenlin Ouyang ◽  
Fang Zheng ◽  
Jared Y Chew ◽  
Yingmei Pei ◽  
Jinhong Zhou ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Dna Binding ◽  
Crystal Structures ◽  
Response Regulator ◽  
Regulatory System ◽  
Repeat Sequence ◽  
Effector Domain ◽  
Receiver Domain ◽  
Regulation Mechanisms ◽  
Significant Conformational Change

Abstract Staphylococcus aureus ArlRS is a key two-component regulatory system necessary for adhesion, biofilm formation, and virulence. The response regulator ArlR consists of a C-terminal DNA-binding effector domain and an N-terminal receiver domain that is phosphorylated by ArlS, the cognate transmembrane sensor histidine kinase. We demonstrate that the receiver domain of ArlR adopts the canonical α5β5 response regulator assembly, which dimerizes upon activation, using beryllium trifluoride as an aspartate phosphorylation mimic. Activated ArlR recognizes a 20-bp imperfect inverted repeat sequence in the ica operon, which is involved in intercellular adhesion polysaccharide production. Crystal structures of the inactive and activated forms reveal that activation induces a significant conformational change in the β4-α4 and β5-α5-connecting loops, in which the α4 and α5 helices constitute the homodimerization interface. Crystal structures of the DNA-binding ArlR effector domain indicate that it is able to dimerize via a non-canonical β1–β2 hairpin domain swapping, raising the possibility of a new mechanism for signal transduction from the receiver domain to effector domain. Taken together, the current study provides structural insights into the activation of ArlR and its recognition, adding to the diversity of response regulation mechanisms that may inspire novel antimicrobial strategies specifically targeting Staphylococcus.

scholarly journals The Level of AdpA Directly Affects Expression of Developmental Genes in Streptomyces coelicolor

2011 ◽  
Vol 193 (22) ◽  
pp. 6358-6365 ◽  
Author(s):  
Marcin Wolański ◽  
Rafał Donczew ◽  
Agnieszka Kois-Ostrowska ◽  
Paweł Masiewicz ◽  
Dagmara Jakimowicz ◽  
...  
Keyword(s):  
Early Stage ◽  
Response Regulator ◽  
Streptomyces Coelicolor ◽  
Streptomyces Griseus ◽  
Morphological Differentiation ◽  
Aerial Mycelium ◽  
Content Type ◽  
Protein Functions

AdpA is a key regulator of morphological differentiation inStreptomyces. In contrast toStreptomyces griseus, relatively little is known about AdpA protein functions inStreptomyces coelicolor. Here, we report for the first time the translation accumulation profile of theS. coelicoloradpA(adpASc) gene; the level ofS. coelicolorAdpA (AdpASc) increased, reaching a maximum in the early stage of aerial mycelium formation (after 36 h), and remained relatively stable for the next several hours (48 to 60 h), and then the signal intensity decreased considerably. AdpAScspecifically binds theadpAScpromoter regionin vitroandin vivo, suggesting that its expression is autoregulated; surprisingly, in contrast toS. griseus, the protein presumably acts as a transcriptional activator. We also demonstrate a direct influence of AdpAScon the expression of several genes whose products play key roles in the differentiation ofS. coelicolor: STI, a protease inhibitor; RamR, an atypical response regulator that itself activates expression of the genes for a small modified peptide that is required for aerial growth; and ClpP1, an ATP-dependent protease. The diverse influence of AdpAScprotein on the expression of the analyzed genes presumably results mainly from different affinities of AdpAScprotein to individual promoters.

scholarly journals Crystal Structure of the Response Regulator 02 Receiver Domain, the Essential YycF Two-Component System of Streptococcus pneumoniae in both Complexed and Native States

2004 ◽  
Vol 186 (9) ◽  
pp. 2872-2879 ◽  
Author(s):  
Colin J. Bent ◽  
Neil W. Isaacs ◽  
Timothy J. Mitchell ◽  
Alan Riboldi-Tunnicliffe
Keyword(s):  
Streptococcus Pneumoniae ◽  
Active Site ◽  
Response Regulator ◽  
Thermotoga Maritima ◽  
Two Component System ◽  
Environmental Signals ◽  
Receiver Domain ◽  
Two Component ◽  
Protein Sequence Homology ◽  
Two Component Signal Transduction

ABSTRACT A variety of bacterial cellular responses to environmental signals are mediated by two-component signal transduction systems comprising a membrane-associated histidine protein kinase and a cytoplasmic response regulator (RR), which interpret specific stimuli and produce a measured physiological response. In RR activation, transient phosphorylation of a highly conserved aspartic acid residue drives the conformation changes needed for full activation of the protein. Sequence homology reveals that RR02 from Streptococcus pneumoniae belongs to the OmpR subfamily of RRs. The structures of the receiver domains from four members of this family, DrrB and DrrD from Thermotoga maritima, PhoB from Escherichia coli, and PhoP from Bacillus subtilis, have been elucidated. These domains are globally very similar in that they are composed of a doubly wound α5β5; however, they differ remarkably in the fine detail of the β4-α4 and α4 regions. The structures presented here reveal a further difference of the geometry in this region. RR02 is has been shown to be the essential RR in the gram-positive bacterium S. pneumoniae R. Lange, C. Wagner, A. de Saizieu, N. Flint, J. Molnos, M. Stieger, P. Caspers, M. Kamber, W. Keck, and K. E. Amrein, Gene 237:223-234, 1999; J. P. Throup, K. K. Koretke, A. P. Bryant, K. A. Ingraham, A. F. Chalker, Y. Ge, A. Marra, N. G. Wallis, J. R. Brown, D. J. Holmes, M. Rosenberg, and M. K. Burnham, Mol. Microbiol. 35:566-576, 2000). RR02 functions as part of a phosphotransfer system that ultimately controls the levels of competence within the bacteria. Here we report the native structure of the receiver domain of RR02 from serotype 4 S. pneumoniae (as well as acetate- and phosphate-bound forms) at different pH levels. Two native structures at 2.3 Å, phased by single-wavelength anomalous diffraction (xenon SAD), and 1.85 Å and a third structure at pH 5.9 revealed the presence of a phosphate ion outside the active site. The fourth structure revealed the presence of an acetate molecule in the active site.

scholarly journals Crystallization and preliminary X-ray analysis of the receiver domain of a putative response regulator, BPSL0128, fromBurkholderia pseudomallei

2012 ◽  
Vol 68 (8) ◽  
pp. 917-922
Author(s):  
Abd Ghani Abd Aziz ◽  
Svetlana E. Sedelnikova ◽  
Sergey N. Ruzheinikov ◽  
Simon Thorpe ◽  
Rahmah Mohamed ◽  
...  
Keyword(s):  
Response Regulator ◽  
X Ray ◽  
Receiver Domain

scholarly journals Biochemical Activities of the absA Two-Component System of Streptomyces coelicolor

2005 ◽  
Vol 187 (2) ◽  
pp. 687-696 ◽  
Author(s):  
Nancy L. Sheeler ◽  
Susan V. MacMillan ◽  
Justin R. Nodwell
Keyword(s):  
Transcriptional Repression ◽  
Kinase Activity ◽  
Response Regulator ◽  
Streptomyces Coelicolor ◽  
Point Mutations ◽  
Stable State ◽  
Sensor Kinase ◽  
Two Component System ◽  
Antibiotic Synthesis ◽  
Cognate Response Regulator

ABSTRACT The AbsA1 sensor kinase and its cognate response regulator AbsA2 are important regulators of antibiotic synthesis in Streptomyces coelicolor. While certain point mutations in absA1 reduce or eliminate the synthesis of several antibiotics, null mutations in these genes bring about enhanced antibiotic synthesis. We show here that AbsA1, which is unusual in sequence and structure, is both an AbsA2 kinase and an AbsA2∼P phosphatase. The half-life of AbsA2∼P in solution is 68.6 min, consistent with a role in maintaining a relatively stable state of transcriptional repression or activation. We find that mutations in the absA locus that enhance antibiotic synthesis impair AbsA2 kinase activity and that mutations that repress antibiotic synthesis impair AbsA2∼P phosphatase activity. These results support a model in which the phosphorylation state of AbsA2 is determined by the balance of the kinase and phosphatase activities of AbsA1 and where AbsA2∼P represses antibiotic biosynthetic genes either directly or indirectly.

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