2Y0Q: The Mechanisms Of Hamp-Mediated Signaling In Transmembrane Receptors - The A291c Mutant

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.
PDB ID: 2Y0QDownload
MMDB ID: 89481
PDB Deposition Date: 2010/12/7
Updated in MMDB: 2011/11
Experimental Method:
x-ray diffraction
Resolution: 2  Å
Source Organism:
Similar Structures:
Biological Unit for 2Y0Q: dimeric; determined by author and by software (PISA)
Molecular Components in 2Y0Q
Label Count Molecule
Proteins (2 molecules)
Uncharacterized Protein
Molecule annotation
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Citing MMDB