Cited by 416Protein Structure and DynamicsBacterial Genetics and BiotechnologyReceptor Mechanisms and Signaling

The HAMP Domain Structure Implies Helix Rotation in Transmembrane Signaling

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Hulko, Michael, Berndt, Franziska, Gruber, Markus, Linder, Jürgen U., Truffault, Vincent, Schultz, Anita, Martin, Jörg, Schultz, Joachim E. +2 more·2006·Cell

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.

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Crossref · 10.1016/j.cell.2006.06.058

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Authors
Hulko, M., Berndt, F., Gruber, M., Linder, J. U., Truffault, V., Schultz, A., Martin, J., Schultz, J. E., Lupas, A. N., & Coles, M.
Affiliations
  • Max Planck Institute for Developmental Biology (DE)
  • University of Tübingen (DE)
Corresponding author
Lupas, Andrei N.
Venue
Cell
Publisher
Elsevier BV
Published
2006-09
Volume
126
Issue
5
Pages
929-940
ISSN
0092-8674 (ISSN-L)
OpenAlex
W2068254342
Cited by
416
References
46
Citations by year
2026: 11 · 2025: 8 · 2024: 7 · 2023: 9 · 2022: 6 · 2021: 23 · 2020: 19 · 2019: 15 · 2018: 16 · 2017: 27 · 2016: 18 · 2015: 18 · 2014: 36 · 2013: 30 · 2012: 19
FWCI
11.75
Type
journal article
Language
en
Open access
Locations
  • Cell (publishedVersion)
  • PubMed (publishedVersion)
  • Max Planck Institute for Plasma Physics (submittedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
Keywords
HAMP domain, helix rotation, transmembrane signaling, signal transduction, coiled coil, histidine kinase, adenylate cyclase, chemotaxis receptor, homodimer, side chain size, conformational equilibrium, protein structure
MeSH terms
Adenosine Triphosphate, Adenylyl Cyclases, Amino Acid Sequence, Bacterial Proteins, Chemoreceptor Cells, Chemotaxis, Escherichia coli, Membrane Proteins, Models, Molecular, Molecular Sequence Data, Mutation, Protein Denaturation, Receptors, Cell Surface, Recombinant Fusion Proteins, Signal Transduction, Protein Structure, Tertiary, Archaeoglobus fulgidus, Archaeal Proteins, Nuclear Magnetic Resonance, Biomolecular, Catalytic Domain, Escherichia coli Proteins

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