Structure of the entire cytoplasmic portion of a sensor histidine-kinase protein

Marina, Alberto; Waldburger, Carey D.; Hendrickson, Wayne A.

doi:10.1038/sj.emboj.7600886

Cited by 273 publications

(367 citation statements)

References 53 publications

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“…The residues corresponding to Pro-410 and Phe-436 in the histidine kinase TM0853 from Thermotoga maritima lie in the first and second alpha-helices of the DHp domain and share contacts with residues in the hydrophobic core of the DHp domain (Marina et al, 2005). We consequently asked if KinA carrying both the P410L and F436S substitutions would have a lower affinity for Sda than the single mutant proteins.…”

Section: The Replacement Of Phe-436 With Serine Increases the Activitmentioning

confidence: 99%

“…Based on a sequence alignment of KinA with the TM0853 histidine kinase from T. maritima for which a high-resolution X-ray structure is available (Marina et al, 2005), we found that the T. maritima residues corresponding to Ala-413 and Tyr-431 are also surface exposed and lie very close to each other on the same face of the DHp domain as the conserved histidine corresponding to KinA His-405, the site of autophosphorylation (Fig. 6).…”

Section: Sda Binding Decreases the Solvent Accessibility Of Residues mentioning

confidence: 99%

“…We therefore used protein crosslinking to ask if Sda bound near Ala-413 or Tyr-431. We performed the cross-linking assays using the kinase domain of KinA fused to an N-terminal hexahistidine tag (his 6-KinA 383-606 ), which, unlike full-length KinA, does not (Tomomori et al, 1999;Marina et al, 2005). KinA residues Pro-410, Ala-413, Tyr-431 and Phe-436 are indicated with arrows.…”

Section: Sda Is Specifically Cross-linked Via a 10 å Linker To Cysteimentioning

confidence: 99%

“…5A) is summarized with circles: white, not accessible; grey, partially accessible; black, accessible. For comparison, the fraction solvent accessibilities for residues of TM0853 calculated from the crystal structure by Marina et al (2005) are indicated: white, < 0.1; grey, 0.1-0.4; black, > 0.4. UniProt accession numbers are: KinA (P16497), KinB (P16449), KinC (P39764), TM0853 (Q9WZV7), EnvZ (P0AEJ4).…”

Section: Sda Is Specifically Cross-linked Via a 10 å Linker To Cysteimentioning

confidence: 99%

“…B. Surface representation of TM0853 (PDB 2C2A; Marina et al, 2005). Residues are labelled with the corresponding KinA residue names and numbers, based on the sequence alignment in (A).…”

Section: Sda Is Specifically Cross-linked Via a 10 å Linker To Cysteimentioning

confidence: 99%

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The histidine kinase inhibitor Sda binds near the site of autophosphorylation and may sterically hinder autophosphorylation and phosphotransfer to Spo0F

Cunningham

Burkholder²

2009

Molecular Microbiology

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SummaryHistidine kinases are widely used by bacteria, fungi and plants to sense and respond to changing environmental conditions. Signals in addition to those directly sensed by the kinase are often integrated by proteins that fine-tune the biological response by modulating the activity of the kinase or its targets. The Bacillus subtilis histidine kinase KinA promotes the initiation of sporulation when nutrients are limiting, but sporulation can be delayed by two inhibitors of KinA, Sda (when DNA replication is perturbed) or KipI (under unknown conditions). We have identified residues in the dimerization/histidinephosphotransfer (DHp) domain of KinA that are functionally important for inhibition by Sda and KipI and overlapping surface-exposed residues that lie close to or comprise the Sda binding site. Sda inhibits the intermolecular transfer of phosphate from the catalytic ATP-binding (CA) domain of KinA to the autophosphorylation site in the DHp domain when the domains are split into separate polypeptides, either by steric hindrance or by altering the conformation of the DHp domain. Sda also slows the rate of phosphotransfer from KinA~P to its target, Spo0F, consistent with our finding that a KinA residue important for Sda function overlaps with the predicted Spo0F binding site on KinA.

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Section: The Replacement Of Phe-436 With Serine Increases the Activitmentioning

confidence: 99%

Section: Sda Binding Decreases the Solvent Accessibility Of Residues mentioning

confidence: 99%

Section: Sda Is Specifically Cross-linked Via a 10 å Linker To Cysteimentioning

confidence: 99%

Section: Sda Is Specifically Cross-linked Via a 10 å Linker To Cysteimentioning

confidence: 99%

“…B. Surface representation of TM0853 (PDB 2C2A; Marina et al, 2005). Residues are labelled with the corresponding KinA residue names and numbers, based on the sequence alignment in (A).…”

Section: Sda Is Specifically Cross-linked Via a 10 å Linker To Cysteimentioning

confidence: 99%

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The histidine kinase inhibitor Sda binds near the site of autophosphorylation and may sterically hinder autophosphorylation and phosphotransfer to Spo0F

Cunningham

Burkholder²

2009

Molecular Microbiology

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Regulatory Systems: Two‐Component

Raivio

2019

Encyclopedia of Life Sciences

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Two‐component signal transduction (TCST) systems constitute a large class of regulatory proteins that function as signal transducers. Each system comprises a sensor or histidine kinase (HK) and an effector or response regulator (RR), which communicate through a conserved set of phosphotransfer reactions to effect adaptive changes in response to specific environmental signals. HKs and RRs are modular in nature, with variable sensory and output structures appended to the conserved domains that facilitate phosphotransfer mediated signal transduction. Input signals trigger successive conformational changes in domains and protein:protein interactions that alter phosphotransfer, and ultimately an output response mediated by the phosphorylated RR. TCST systems are abundant in bacteria and many microbes utilise multiple TCST pathways to sense and respond to a plethora of environmental and physiological changes. Specificity between cognate HKs and RRs is largely maintained through co‐evolving residues at a conserved interface where the RR docks on the HK. TCST systems are integrated into cellular signalling networks and interact with macromolecules and proteins that connect them to salient regulatory pathways and cellular functions. The current state of knowledge around TCST systems will be summarised, emphasising findings published since the first version of this article in 2006. Key Concepts A prototypical two‐component system is made up of a membrane‐bound sensory histidine kinase that senses a unique environmental or cellular parameter and a cytoplasmic response regulator that controls an adaptive response. HKs and RRs communicate through phosphotransfer reactions that are mediated by conserved domains; signal sensing alters the ratio of HK kinase to phosphatase activity to change the function of the RR by altering its phosphorylation status. HKs and RRs are organised in a modular fashion; a variety of sensing domains can be appended to the HK enzymatic module while diverse output domains with DNA binding, RNA binding, enzymatic activity or protein binding functions are often fused to the C‐terminal end of the response regulator phosphorylated receiver (REC) domain. The HK is a dimer containing a catalytic domain composed of two DHp and CA domains. The DHp domain consists of a d imer of two alpha helices connected by a flexible linker that makes a four‐helical bundle and contains the conserved h istidine that is the site of auto p hosphorylation. The CA domain resembles other ATP‐binding folds and is the enzymatic portion of the HK. The RR consists at its N‐terminus of the conserved receiver (REC) domain, which consists of a five‐stranded beta sheet surrounded by alpha helices and contains the conserved aspartate that is the site of phosphorylation. Signals are detected through conformational changes in a sensory domain that are propagated through some combination of rotational, piston and order to disorder transitions by alpha‐helical transduction elements to the cytoplasmic enzymatic domain of the HK. These movements lead to alterations in HK dimer symmetry that dictate kinase or phosphatase activity. In the inactive state, the cytoplasmic DHp and CA domains of the HK are organised in a symmetrical fashion with the CA domain juxtaposed against the membrane‐proximal end of the DHp four‐helical bundle. The RR REC domain can interact with the inactive HK DHp four‐helical bundle at a more membrane‐distal location in an orientation that would facilitate dephosphorylation of the aspartate. The active, kinase state of the HK is asymmetrical due to a bend or kink in the DHp domain that leads to one CA domain adopting a looser association that positions it well for phosphorylation of a histidine residue. A single RR REC domain can bind near the other CA domain, which is more closely associated with the DHp domain, in a conformation supporting phosphorylation of the aspartate residue utilising the phosphorylated histidine as a substrate. Repeated cycles of DHp domain bending and RR REC domain binding are hypothesised to support successive rounds of HK autophosphorylation and RR phosphorylation in response to signal inputs received from the sensory domain. HKs and RRs regulate and interact with other macromolecules and proteins to connect signalling pathways, coordinate their activities and sense environmental parameters and changes to cellular physiology.

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Understanding Gene Duplication Through Biochemistry and Population Genetics

Liberles

Kolesov

Dittmar

2010

Evolution After Gene Duplication

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Gene duplication has emerged as an important process supporting the functional diversification of genes. Since publication of the seminal book Evolution by Gene Duplication by Ohno (1970), the hypothesis regarding the importance of gene duplication in the generation of evolutionary novelty has steadily gained support as we have entered the genome-sequencing era. It is through the link to functional biology that an ultimate understanding of the preservation and diversification of duplicate genes will be accomplished.Genes can diverge in function through accumulation (fixation) of coding sequence changes, which may influence binding interactions and/or catalysis, through the evolution of splice variants, and through spatial, temporal, and concentration-level changes in the expression of the protein product. Governing these processes is an interplay among mutational opportunity, population dynamics, protein biochemistry, and systems and organismal biology. This interplay is described systematically in this chapter. SYSTEMS BIOLOGY AND HIGHER-LEVEL ORGANIZATIONAt the level of biological systems, two early but still relevant views suggested a role for gene duplication in constructing pathways. These views are both dependent on a new function emerging in one of the duplicates, but differ in the manner in which it occurs. One view, patchwork evolution, involved a conservation of catalytic activity coupled with the evolution of a new substrate after duplication (Jensen, 1976). An alternative view, retrograde evolution, suggested that pathways are built up backward, with product becoming substrate based on recognition of the transition state in the Evolution After Gene Duplication, Edited by Katharina Dittmar and David Liberles

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Structure of the entire cytoplasmic portion of a sensor histidine-kinase protein

Cited by 273 publications

References 53 publications

The histidine kinase inhibitor Sda binds near the site of autophosphorylation and may sterically hinder autophosphorylation and phosphotransfer to Spo0F

The histidine kinase inhibitor Sda binds near the site of autophosphorylation and may sterically hinder autophosphorylation and phosphotransfer to Spo0F

Regulatory Systems: Two‐Component

Understanding Gene Duplication Through Biochemistry and Population Genetics

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