Structure of PAS-Linked Histidine Kinase and the Response Regulator Complex

Yamada, Seiji; Sugimoto, Hiroshi; Kobayashi, Miki; Ohno, Ayako; Nakamura, H.; Shiro, Yoshitsugu

doi:10.1016/j.str.2009.07.016

Cited by 84 publications

(99 citation statements)

References 47 publications

(52 reference statements)

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“…7A). Therefore, PmrD is likely a competitive inhibitor of histidine kinase because it binds with the response regulator at a similar interface surrounding the phosphorylation site (48). In the PmrD-PmrA N complex model, the phosphoacceptor Asp-51 faces the open mouth area of the ␤-barrel of the PmrD structure, which reflects the protection mode of the connector protein on the phosphorylated response regulator.…”

Section: Discussionmentioning

confidence: 99%

“…The binding interface of PmrA N is also similar to that observed in the crystal structure of the DHp domain in the ThkA-TrrA complex and Spo0F in the Spo0B-Spo0F complex from Bacillus subtilis, in which TrrA and Spo0F are the response regulators. In the PmrD-PmrA N complex, the phosphoacceptor Asp-51 in PmrA faces the His-70 of PmrD, similar to the phosphodonor His in the HK DHp domain (His-547 in ThkA) (48,49). Hydrogen bonds and electrostatic interactions are important for stability and specificity of protein-protein interactions (50,51).…”

Section: Discussionmentioning

confidence: 99%

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Structural Basis of a Physical Blockage Mechanism for the Interaction of Response Regulator PmrA with Connector Protein PmrD from Klebsiella pneumoniae

Luo

Lou

Rajasekaran

et al. 2013

Journal of Biological Chemistry

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Background: PmrD binds to phospho-PmrA and sustains its phosphorylation state. Results: Phospho-PmrA interacts with PmrD via several specific intermolecular interactions. Conclusion: A steric inhibition mechanism was proposed for protecting phospho-PmrA against dephosphorylation. Significance: This work provides novel data revealing how a connector protein protects an activated response regulator.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Structural Basis of a Physical Blockage Mechanism for the Interaction of Response Regulator PmrA with Connector Protein PmrD from Klebsiella pneumoniae

Luo

Lou

Rajasekaran

et al. 2013

Journal of Biological Chemistry

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show abstract

“…A complex structure of ThkA/TrrA, also from T. maritima, has a similar binding site on HK for RR [53], and the structure also represents a phosphatase-competent state because the CA domain is locked in a position away from the phosphorylation site histidine. Similar to RR468, TrrA is also a single domain RR.…”

Section: Interactions Between Histidine Kinases and Response Regulatorsmentioning

confidence: 99%

Bacterial Two-Component Systems: Structures and Signaling Mechanisms

Wang¹

2012

Protein Phosphorylation in Human Health

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Protein Phosphorylation in Human Health 440accepting chemotaxis proteins, and Phosphatases [1], hence the name. The HAMP domain connects TM2 to the dimerization and histidine phosphorylation domain (often abbreviated as DHp). A catalytic and ATP-binding (CA) domain lies at the carboxyl terminus. The combination of DHp and CA is sometimes referred to as the kinase domain. The TM helices, HAMP domains, and DHp domains are all involved in homodimerization. The sensor domain is likely to dimerize in the context of the entire protein. Sensor domains share little sequence identity, as is expected from their diverse functions of sensing various signals. However, available structures of sensor domains fall into a few common structural folds, suggesting conserved signal sensing mechanisms. The HAMP, DHp, and CA domains are common modules of HKs and have well conserved structures and sequences, especially DHp and CA, whose sequences contain several conserved motifs. There is an absolutely conserved histidine residue that is phosphorylated, and the phosphoryl group is then donated to an RR, in response to signals sensed by the sensor domain. How the sensor domain regulates the kinase activities is still unknown, due to the lack of full-length structures of the transmembrane sensor HKs. However, a large accumulation of structures of isolated domains in recent years has started to shed light on possible molecular mechanisms of the signal transduction. In this section, I will summarize these structures and discuss their conformational changes that transmit signals from the sensor domain to the kinase domain. Structures of sensor domainsSensor domains of histidine kinases are located in cytosol, in membrane, or outside of cell membrane (extracytosolic). Currently, there is little structural information of the membraneBacterial Two-Component Systems: Structures and Signaling Mechanisms 441 embedded sensor domains. The prototypical HK has an extracytosolic sensor domain that senses extracellular signals or conditions in the cell envelope. These sensor domains have highly diverse sequences. However, most of the known structures of extracytosolic sensor domains fall into three distinct structural folds, mixed , all-helical, and -sandwich. Unlike extracytosolic sensor domains, many cytosolic sensor domains can be annotated on the sequence level as PAS or GAF domains, which have related structural folds and are named from their occurrence in Period circadian, Aryl hydrocarbon receptor nuclear translocator, and Single-minded proteins (PAS) [2], or in cGMP-regulated cyclic nucleotide phosphodiesterases, Adenylate cyclases, and the bacterial transcriptional regulator FhlA (GAF) [3].

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“…3a). Two other structures of kinases and response regulators in complex confirm the central position of the specificity residues at the interaction interface [30,31].…”

Section: Identification and Characterization Of Specificity Residuesmentioning

confidence: 72%

Determinants of specificity in two-component signal transduction

Podgornaia

Laub

2013

Current Opinion in Microbiology

128

133

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Maintaining the faithful flow of information through signal transduction pathways is critical to the survival and proliferation of organisms. This problem is particularly challenging as many signaling proteins are part of large, paralogous families that are highly similar at the sequence and structural levels, increasing the risk of unwanted cross-talk. To detect environmental signals and process information, bacteria rely heavily on two-component signaling systems comprised of sensor histidine kinases and their cognate response regulators. Although most species encode dozens of these signaling pathways, there is relatively little cross-talk, indicating that individual pathways are well insulated and highly specific. Here, we review the molecular mechanisms that enforce this specificity. Further, we highlight recent studies that have revealed how these mechanisms evolve to accommodate the introduction of new pathways by gene duplication.3

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Structure of PAS-Linked Histidine Kinase and the Response Regulator Complex

Cited by 84 publications

References 47 publications

Structural Basis of a Physical Blockage Mechanism for the Interaction of Response Regulator PmrA with Connector Protein PmrD from Klebsiella pneumoniae

Structural Basis of a Physical Blockage Mechanism for the Interaction of Response Regulator PmrA with Connector Protein PmrD from Klebsiella pneumoniae

Bacterial Two-Component Systems: Structures and Signaling Mechanisms

Determinants of specificity in two-component signal transduction

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