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The Mechanisms of HAMP-Mediated Signaling in Transmembrane Receptors
- Source :
- Structure. (3):378-385
- Publisher :
- Elsevier Ltd.
-
Abstract
- SummaryHAMP 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.
- Subjects :
- Models, Molecular
Archaeal Proteins
Amino Acid Motifs
Biology
Crystallography, X-Ray
Chimerism
Mycobacterium
HAMP domain
Adenylyl cyclase
chemistry.chemical_compound
Structure-Activity Relationship
Bacterial Proteins
Cell surface receptor
Structural Biology
Molecular Biology
Coiled coil
Membrane Proteins
Ligand (biochemistry)
Protein Structure, Tertiary
Biochemistry
chemistry
Archaeoglobus fulgidus
Helix
Mutation
Biophysics
HAMP
Signal transduction
Crystallization
Adenylyl Cyclases
Signal Transduction
Subjects
Details
- Language :
- English
- ISSN :
- 09692126
- Issue :
- 3
- Database :
- OpenAIRE
- Journal :
- Structure
- Accession number :
- edsair.doi.dedup.....155088ca4209fcfb0b8d9825722bdf53
- Full Text :
- https://doi.org/10.1016/j.str.2011.01.006