The Mechanisms of HAMP-Mediated Signaling in Transmembrane Receptors
HAMP domains mediate signal transduction in over 7500 enzyme-coupled receptors represented in all kingdoms of life. The HAMP domain of the putative archaeal receptor Af1503 has a parallel, dimeric, four-helical coiled coil structure, but with unusual core packing, related to canonical packing by con...
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| Veröffentlicht in: | Structure (London) 2011-03, Vol.19 (3), p.378-385 |
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| creator | Ferris, Hedda U. Dunin-Horkawicz, Stanislaw Mondéjar, Laura García Hulko, Michael Hantke, Klaus Martin, Jörg Schultz, Joachim E. Zeth, Kornelius Lupas, Andrei N. Coles, Murray |
| description | HAMP domains mediate signal transduction in over 7500 enzyme-coupled receptors represented in all kingdoms of life. The HAMP domain of the putative archaeal receptor Af1503 has a parallel, dimeric, four-helical coiled coil structure, but with unusual core packing, related to canonical packing by concerted axial rotation of the helices. This has led to the gearbox model for signal transduction, whereby the alternate packing modes correspond to signaling states. Here we present structures of a series of Af1503 HAMP variants. We show that substitution of a conserved small side chain within the domain core (A291) for larger residues induces a gradual transition in packing mode, involving both changes in helix rotation and bundle shape, which are most prominent at the C-terminal, output end of the domain. These are correlated with activity and ligand response in vitro and in vivo by incorporating Af1503 HAMP into mycobacterial adenylyl cyclase assay systems.
► Residue substitutions in the HAMP domain core induce axial helix rotation ► Helix rotation can be correlated with activity in vitro and in vivo ► HAMP domain output includes both changes in rotation state and bundle radius ► Supports the gearbox model of signal transduction via axial helix rotation |
| doi_str_mv | 10.1016/j.str.2011.01.006 |
| format | Article |
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Dunin-Horkawicz, Stanislaw ; Mondéjar, Laura García ; Hulko, Michael ; Hantke, Klaus ; Martin, Jörg ; Schultz, Joachim E. ; Zeth, Kornelius ; Lupas, Andrei N. ; Coles, Murray</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c493t-3afaa5a100425ea253d78ccf680897ece909c0376dd27620c0dc73e4431ea5923</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>Adenylyl Cyclases - metabolism</topic><topic>Amino Acid Motifs</topic><topic>Archaeal Proteins - chemistry</topic><topic>Archaeal Proteins - genetics</topic><topic>Archaeal Proteins - metabolism</topic><topic>Archaeoglobus fulgidus - chemistry</topic><topic>Bacterial Proteins - chemistry</topic><topic>Bacterial Proteins - genetics</topic><topic>Bacterial Proteins - metabolism</topic><topic>Biomedical materials</topic><topic>Chimerism</topic><topic>Coiling</topic><topic>Crystallization</topic><topic>Crystallography, X-Ray</topic><topic>Gearboxes</topic><topic>In vivo testing</topic><topic>In vivo tests</topic><topic>Ligands</topic><topic>Membrane Proteins - chemistry</topic><topic>Membrane Proteins - genetics</topic><topic>Membrane Proteins - metabolism</topic><topic>Models, Molecular</topic><topic>Mutation</topic><topic>Mycobacterium - chemistry</topic><topic>Protein Structure, Tertiary - genetics</topic><topic>Receptors</topic><topic>Residues</topic><topic>Signal Transduction</topic><topic>Structure-Activity Relationship</topic><topic>Surgical implants</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ferris, Hedda U.</creatorcontrib><creatorcontrib>Dunin-Horkawicz, Stanislaw</creatorcontrib><creatorcontrib>Mondéjar, Laura García</creatorcontrib><creatorcontrib>Hulko, Michael</creatorcontrib><creatorcontrib>Hantke, Klaus</creatorcontrib><creatorcontrib>Martin, Jörg</creatorcontrib><creatorcontrib>Schultz, Joachim E.</creatorcontrib><creatorcontrib>Zeth, Kornelius</creatorcontrib><creatorcontrib>Lupas, Andrei N.</creatorcontrib><creatorcontrib>Coles, Murray</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>Solid State and Superconductivity Abstracts</collection><collection>Technology Research Database</collection><collection>ANTE: Abstracts in New Technology & Engineering</collection><collection>Engineering Research Database</collection><collection>Advanced Technologies Database with Aerospace</collection><jtitle>Structure (London)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ferris, Hedda U.</au><au>Dunin-Horkawicz, Stanislaw</au><au>Mondéjar, Laura García</au><au>Hulko, Michael</au><au>Hantke, Klaus</au><au>Martin, Jörg</au><au>Schultz, Joachim E.</au><au>Zeth, Kornelius</au><au>Lupas, Andrei N.</au><au>Coles, Murray</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The Mechanisms of HAMP-Mediated Signaling in Transmembrane Receptors</atitle><jtitle>Structure (London)</jtitle><addtitle>Structure</addtitle><date>2011-03-09</date><risdate>2011</risdate><volume>19</volume><issue>3</issue><spage>378</spage><epage>385</epage><pages>378-385</pages><issn>0969-2126</issn><eissn>1878-4186</eissn><abstract>HAMP domains mediate signal transduction in over 7500 enzyme-coupled receptors represented in all kingdoms of life. 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► Residue substitutions in the HAMP domain core induce axial helix rotation ► Helix rotation can be correlated with activity in vitro and in vivo ► HAMP domain output includes both changes in rotation state and bundle radius ► Supports the gearbox model of signal transduction via axial helix rotation</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>21397188</pmid><doi>10.1016/j.str.2011.01.006</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; Cell Press Free Archives; ScienceDirect Journals (5 years ago - present); EZB-FREE-00999 freely available EZB journals; Free Full-Text Journals in Chemistry |
| subjects | Adenylyl Cyclases - metabolism Amino Acid Motifs Archaeal Proteins - chemistry Archaeal Proteins - genetics Archaeal Proteins - metabolism Archaeoglobus fulgidus - chemistry Bacterial Proteins - chemistry Bacterial Proteins - genetics Bacterial Proteins - metabolism Biomedical materials Chimerism Coiling Crystallization Crystallography, X-Ray Gearboxes In vivo testing In vivo tests Ligands Membrane Proteins - chemistry Membrane Proteins - genetics Membrane Proteins - metabolism Models, Molecular Mutation Mycobacterium - chemistry Protein Structure, Tertiary - genetics Receptors Residues Signal Transduction Structure-Activity Relationship Surgical implants |
| title | The Mechanisms of HAMP-Mediated Signaling in Transmembrane Receptors |
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