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Biology Direct

, 1:25

First Online: 05 September 2006Received: 21 July 2006Accepted: 05 September 2006


BackgroundThe mechanism by which the signals are transmitted between receptor and effector domains in multi-domain signaling proteins is poorly understood.

ResultsUsing sensitive sequence analysis methods we identify a conserved helical segment of around 40 residues in a wide range of signaling proteins, including numerous sensor histidine kinases such as Sln1p, and receptor guanylyl cyclases such as the atrial natriuretic peptide receptor and nitric oxide receptors. We term this helical segment the signaling S-helix and present evidence that it forms a novel parallel coiled-coil element, distinct from previously known helical segments in signaling proteins, such as the Dimerization-Histidine phosphotransfer module of histidine kinases, the intra-cellular domains of the chemotaxis receptors, inter-GAF domain helical linkers and the α-helical HAMP module. Analysis of domain architectures allowed us to reconstruct the domain-neighborhood graph for the S-helix, which showed that the S-helix almost always occurs between two signaling domains. Several striking patterns in the domain neighborhood of the S-helix also became evident from the graph. It most often separates diverse N-terminal sensory domains from various C-terminal catalytic signaling domains such as histidine kinases, cNMP cyclase, PP2C phosphatases, NtrC-like AAA+ ATPases and diguanylate cyclases. It might also occur between two sensory domains such as PAS domains and occasionally between a DNA-binding HTH domain and a sensory domain. The sequence conservation pattern of the S-helix revealed the presence of a unique constellation of polar residues in the dimer-interface positions within the central heptad of the coiled-coil formed by the S-helix.

ConclusionCombining these observations with previously reported mutagenesis studies on different S-helix-containing proteins we suggest that it functions as a switch that prevents constitutive activation of linked downstream signaling domains. However, upon occurrence of specific conformational changes due to binding of ligand or other sensory inputs in a linked upstream domain it transmits the signal to the downstream domain. Thus, the S-helix represents one of the most prevalent functional themes involved in the flow of signals between modules in diverse prokaryote-type multi-domain signaling proteins.

ReviewersThis article was reviewed by Frank Eisenhaber, Arcady Mushegian and Sandor Pongor.

AbbreviationsS-helixSignaling Helix

CCCoiled Coil

H-KinasesHistidine Kinases

DHpdimerization and histidine phosphotransfer

bZIPbasic-leucine zipper

PSSMsposition specific score matrices


HNOBHeme NO Binding domain

HNOBAHNOB Associated domain

HPThistidine-containing phosphotransfer domain

MAMethyl Acceptor domain

PASPer-Arnt Sim domain

MCPNMethyl Acceptor Chemotaxis protein N-terminal domain

KH-KHomology RNA binding domain

Electronic supplementary materialThe online version of this article doi:10.1186-1745-6150-1-25 contains supplementary material, which is available to authorized users.

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Autor: Vivek Anantharaman - S Balaji - L Aravind


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