Taxonomic distribution of proteins containing HAMP domains

The tree below includes only several representative species and genera. The complete taxonomic breakdown of all proteins containing HAMP domains can be accessed here. Click the counts or percentage values to display the corresponding proteins.

The cytoplasmic helical linker domain of receptor histidine kinase and methyl-accepting proteins is common to many prokaryotic signalling proteins.

Aravind L, Ponting CP
FEMS Microbiol Lett. 1999; 176: 111-6

Mutations in the cytoplasmic linker regions of receptor histidine kinase and chemoreceptor proteins have been shown previously to significantly impair receptor functions. Here we demonstrate significant sequence similarities between these regions in numerous histidine kinases, methyl-accepting proteins, adenylyl cyclases and other prokaryotic signalling proteins. It is suggested that these 'HAMP domains' possess roles of regulating the phosphorylation or methylation of homodimeric receptors by transmitting the conformational changes in periplasmic ligand-binding domains to cytoplasmic signalling kinase and methyl-acceptor domains.

Functional similarities among two-component sensors and methyl-accepting chemotaxis proteins suggest a role for linker region amphipathic helices in transmembrane signal transduction.

Williams SB, Stewart V
Mol Microbiol. 1999; 33: 1093-102

Signal-responsive components of transmembrane signal-transducing regulatory systems include methyl-accepting chemotaxis proteins and membrane-bound, two-component histidine kinases. Prokaryotes use these regulatory networks to channel environmental cues into adaptive responses. A typical network is highly discriminating, using a specific phosphoryl relay that connects particular signals to appropriate responses. Current understanding of transmembrane signal transduction includes periplasmic signal binding with the subsequent conformational changes being transduced, via transmembrane helix movements, into the sensory protein's cytoplasmic domain. These induced conformational changes bias the protein's regulatory function. Although the mutational analyses reviewed here identify a role for the linker region in transmembrane signal transduction, no specific mechanism of linker function has yet been described. We propose a speculative, mechanistic model for linker function based on interactions between two putative amphipathic helices. The model attempts to explain both mutant phenotypes and hybrid sensor data, while accounting for recognized features of amphipathic helices.

Computational learning reveals coiled coil-like motifs in histidine kinase linker domains.

Singh M, Berger B, Kim PS, Berger JM, Cochran AG
Proc Natl Acad Sci U S A. 1998; 95: 2738-43

The recent rapid growth of protein sequence databases is outpacing the capacity of researchers to biochemically and structurally characterize new proteins. Accordingly, new methods for recognition of motifs and homologies in protein primary sequences may be useful in determining how these proteins might function. We have applied such a method, an iterative learning algorithm, to analyze possible coiled coil domains in histidine kinase receptors. The potential coiled coils have not yet been structurally characterized in any histidine kinase, and they appear outside previously noted kinase homology regions. The learning algorithm uses a combination of established sequence patterns in known coiled coil proteins and histidine kinase sequence data to learn to recognize efficiently this coiled coil-like motif in the histidine kinases. The common appearance of the structural motif in a functionally important part of the receptors suggests hypotheses for kinase regulation and signal transduction.