Formation of a Novel Four-Helix Bundle and Molecular Recognition Sites by Dimerization of a Response Regulator Phosphotransferase

Varughese, Kottayil I.; Madhusudan, M. D.; Zhou, Xiao Zhen; Whiteley, John M.; Hoch, James A.

doi:10.1016/s1097-2765(00)80148-3

Cited by 112 publications

(89 citation statements)

References 36 publications

(14 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…1 A-C) shows the characteristic homodimeric structure observed in other HKs (8). Each monomer consists of an N-terminal antiparallel 2-helix hairpin (helices ␣1 and ␣2) that includes the phoshorylatable H188, connected by a short linker region (residues 243-245) to a C-terminal ATP-binding domain (ABD).…”

Section: Resultsmentioning

confidence: 96%

Structural plasticity and catalysis regulation of a thermosensor histidine kinase

Albanesi

Martín

Trajtenberg

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

159

258

View full text Add to dashboard Cite

Temperature sensing is essential for the survival of living cells. A major challenge is to understand how a biological thermometer processes thermal information to optimize cellular functions. Using structural and biochemical approaches, we show that the thermosensitive histidine kinase, DesK, from Bacillus subtilis is coldactivated through specific interhelical rearrangements in its central four-helix bundle domain. As revealed by the crystal structures of DesK in different functional states, the plasticity of this helical domain influences the catalytic activities of the protein, either by modifying the mobility of the ATP-binding domains for autokinase activity or by modulating binding of the cognate response regulator to sustain the phosphotransferase and phosphatase activities. The structural and biochemical data suggest a model in which the transmembrane sensor domain of DesK promotes these structural changes through conformational signals transmitted by the membrane-connecting two-helical coiled-coil, ultimately controlling the alternation between output autokinase and phosphatase activities. The structural comparison of the different DesK variants indicates that incoming signals can take the form of helix rotations and asymmetric helical bends similar to those reported for other sensing systems, suggesting that a similar switching mechanism could be operational in a wide range of sensor histidine kinases.coiled-coil ͉ conformational rearrangement ͉ crystallography ͉ signal transduction

show abstract

Section: Resultsmentioning

confidence: 96%

Structural plasticity and catalysis regulation of a thermosensor histidine kinase

Albanesi

Martín

Trajtenberg

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

159

258

View full text Add to dashboard Cite

show abstract

“…2B), suggesting that loss of the arginine side chain, instead of the gain of a new side chain characteristic, was responsible for receptor activation. Notably, all members of the HPK 10 family of peptidesensing polytopic receptors (18), to which AgrC belongs, contain an R or a K at the position directly preceding the phosphorylation site histidine, as does the Bacillus subtilis phosphotransferase Spo0B, in which the crystal structure shows the arginine to be part of a salt bridge with a distal glutamate (19). These observations highlight the importance of a positively charged side chain at this position.…”

Section: Resultsmentioning

confidence: 96%

agr receptor mutants reveal distinct modes of inhibition by staphylococcal autoinducing peptides

Geisinger

Muir

Novick

2009

Proc. Natl. Acad. Sci. U.S.A.

102

114

View full text Add to dashboard Cite

Through the agr quorum-sensing system, staphylococci secrete unique autoinducing peptides (AIPs) and detect their concentration via the AgrC transmembrane receptor, coordinating local bacterial population density with global changes in gene expression. Unique AIP and AgrC variants exist within and between species, and although autologous interactions lead to agr activation, heterologous interactions usually lead to cross-inhibition, resulting in natural quorum-sensing interference. To gain insight into the mechanisms responsible for these phenomena at the level of the receptor, we used random mutagenesis to isolate variants of Staphylococcus aureus AgrC-I with constitutive activity. Constitutive mutations in the sensor domain of the receptor were localized to the last transmembrane helix, whereas those in the histidine kinase domain were mostly clustered to a region near the phosphorylation site histidine. Analysis of these mutants with a range of noncognate AIPs revealed that inhibition is manifested by inverse agonism in certain heterologous pairings and by neutral antagonism in others. In addition, we isolated and characterized an AgrC sensor domain mutant with dramatically broadened activation specificity and reduced sensitivity to inhibition, identifying a single amino acid as a critical determinant of ligand-mediated inhibition. These results suggest that certain noncognate AIPs stabilize an inhibitory receptor conformation that may be a critical feature of the ligand-receptor interaction not initially appreciated in previous analyses of agr inhibition.constitutive mutant ͉ inverse agonism ͉ staphylococci ͉ quorum sensing

show abstract

“…The intra-subunit interface is mostly hydrophobic; the dimer interface, however, contains two acidic clusters. A related phosphotransferase Spo0B from B. subtilis has a similar dimerization domain of four-helix bundle [20]. The active site residue H30 is in the middle of helix D1, with its side chain protruding to the surface, similar to that of the EnvZ DHp domain.…”

Section: The Dimerization and Phosphorylation Domainmentioning

confidence: 99%

Bacterial Two-Component Systems: Structures and Signaling Mechanisms

Wang¹

2012

Protein Phosphorylation in Human Health

View full text Add to dashboard Cite

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].

show abstract

Formation of a Novel Four-Helix Bundle and Molecular Recognition Sites by Dimerization of a Response Regulator Phosphotransferase

Cited by 112 publications

References 36 publications

Structural plasticity and catalysis regulation of a thermosensor histidine kinase

Structural plasticity and catalysis regulation of a thermosensor histidine kinase

agr receptor mutants reveal distinct modes of inhibition by staphylococcal autoinducing peptides

Bacterial Two-Component Systems: Structures and Signaling Mechanisms

Contact Info

Product

Resources

About