title: The HAMP domain structure implies helix rotation in transmembrane signaling.
abstract: HAMP domains connect extracellular sensory with intracellular signaling domains in over 7500 proteins, including histidine kinases, adenylyl cyclases, chemotaxis receptors, and phosphatases. The solution structure of an archaeal HAMP domain shows a homodimeric, four-helical, parallel coiled coil with unusual interhelical packing, related to the canonical packing by rotation of the helices. This suggests a model for the mechanism of signal transduction, in which HAMP alternates between the observed conformation and a canonical coiled coil. We explored this mechanism in vitro and in vivo using HAMP domain fusions with a mycobacterial adenylyl cyclase and an E. coli chemotaxis receptor. Structural and functional studies show that the equilibrium between the two forms is dependent on the side-chain size of residue 291, which is alanine in the wild-type protein.
authors.affiliation: Department of Protein Evolution, Max-Planck-Institute for Developmental Biology, 72076 Tübingen, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Hulko
authors.forename: Franziska
authors.initials: F
authors.lastname: Berndt
authors.forename: Markus
authors.initials: M
authors.lastname: Gruber
authors.forename: Jürgen U
authors.initials: JU
authors.lastname: Linder
authors.forename: Vincent
authors.initials: V
authors.lastname: Truffault
authors.forename: Anita
authors.initials: A
authors.lastname: Schultz
authors.forename: Jörg
authors.initials: J
authors.lastname: Martin
authors.forename: Joachim E
authors.initials: JE
authors.lastname: Schultz
authors.forename: Andrei N
authors.initials: AN
authors.lastname: Lupas
authors.forename: Murray
authors.initials: M
authors.lastname: Coles
mesh_terms: D000255:Adenosine Triphosphate / Q000494:pharmacology; D000262:Adenylyl Cyclases / Q000235:genetics; D000595:Amino Acid Sequence; D019843:Archaeal Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D019611:Archaeoglobus fulgidus; D001426:Bacterial Proteins; D020134:Catalytic Domain; D002628:Chemoreceptor Cells; D002633:Chemotaxis; D004926:Escherichia coli / Q000187:drug effects / Q000378:metabolism; D029968:Escherichia coli Proteins / Q000235:genetics; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation; D019906:Nuclear Magnetic Resonance, Biomolecular; D011489:Protein Denaturation; D017434:Protein Structure, Tertiary; D011956:Receptors, Cell Surface; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D019843:Archaeal Proteins; D001426:Bacterial Proteins; D029968:Escherichia coli Proteins; D008565:Membrane Proteins; D011956:Receptors, Cell Surface; D011993:Recombinant Fusion Proteins; C057331:Tar protein, E coli; D000255:Adenosine Triphosphate; D000262:Adenylyl Cyclases