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          Institute: MPI für Entwicklungsbiologie     Collection: Abteilung 1 - Protein Evolution (A. Lupas)     Display Documents

ID: 591401.0, MPI für Entwicklungsbiologie / Abteilung 1 - Protein Evolution (A. Lupas)
The mechanisms of HAMP-mediated signaling in transmembrane receptors
Authors:Ferris, H. U.; Dunin-Horkawicz, S.; Mondejar, L. G.; Hulko, M.; Hantke, K.; Martin, J.; Schultz, J. E.; Zeth, K.; Lupas, A. N.; Coles, M.
Date of Publication (YYYY-MM-DD):2011-03-09
Title of Journal:Structure
Issue / Number:3
Start Page:378
End Page:385
Review Status:not specified
Audience:Not Specified
Abstract / 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.
Free Keywords:Adenylate Cyclase/metabolism; Amino Acid Motifs; Archaeal Proteins/chemistry/genetics/*metabolism; Archaeoglobus fulgidus/chemistry; Bacterial Proteins/chemistry/genetics/*metabolism; Chimerism; Crystallization; Crystallography, X-Ray; Membrane Proteins/chemistry/genetics/*metabolism; Models, Molecular; Mutation; Mycobacterium/chemistry; Protein Structure, Tertiary/*genetics; *Signal Transduction; Structure-Activity Relationship
External Publication Status:published
Document Type:Article
Affiliations:MPI für Entwicklungsbiologie/Abteilung 1 - Proteinevolution (Andrei Lupas)
External Affiliations:%G eng
Identifiers:ISSN:1878-4186 (Electronic) 0969-2126 (Linking) %R S096... [ID No:1]
URL:http://www.ncbi.nlm.nih.gov/pubmed/21397188 [ID No:2]
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