4I3M

Aer2 poly-HAMP domains: L44H HAMP1 CW-lock mutant

Summary for 4I3M

• Entry DOI: 10.2210/pdb4i3m/pdb
• Related: 3LNR 4I44
• Descriptor: Aerotaxis transducer Aer2, SULFATE ION, SODIUM ION, ... (6 entities in total)
• Functional Keywords: hamp domain, poly-hamp domain, signal transduction, signal relay, signaling protein
• Biological source: Pseudomonas aeruginosa
• Total number of polymer chains: 1
• Total formula weight: 19283.24

Authors

Airola, M.V.,Sukomon, N.,Crane, B.R. (deposition date: 2012-11-26, release date: 2013-02-27, Last modification date: 2024-02-28)

Primary citation

Airola, M.V.,Sukomon, N.,Samanta, D.,Borbat, P.P.,Freed, J.H.,Watts, K.J.,Crane, B.R.
HAMP Domain Conformers That Propagate Opposite Signals in Bacterial Chemoreceptors.
Plos Biol., 11:e1001479-e1001479, 2013

PubMed Abstract: HAMP domains are signal relay modules in >26,000 receptors of bacteria, eukaryotes, and archaea that mediate processes involved in chemotaxis, pathogenesis, and biofilm formation. We identify two HAMP conformations distinguished by a four- to two-helix packing transition at the C-termini that send opposing signals in bacterial chemoreceptors. Crystal structures of signal-locked mutants establish the observed structure-to-function relationships. Pulsed dipolar electron spin resonance spectroscopy of spin-labeled soluble receptors active in cells verify that the crystallographically defined HAMP conformers are maintained in the receptors and influence the structure and activity of downstream domains accordingly. Mutation of HR2, a key residue for setting the HAMP conformation and generating an inhibitory signal, shifts HAMP structure and receptor output to an activating state. Another HR2 variant displays an inverted response with respect to ligand and demonstrates the fine energetic balance between "on" and "off" conformers. A DExG motif found in membrane proximal HAMP domains is shown to be critical for responses to extracellular ligand. Our findings directly correlate in vivo signaling with HAMP structure, stability, and dynamics to establish a comprehensive model for HAMP-mediated signal relay that consolidates existing views on how conformational signals propagate in receptors. Moreover, we have developed a rational means to manipulate HAMP structure and function that may prove useful in the engineering of bacterial taxis responses.

PubMed: 23424282
DOI: 10.1371/journal.pbio.1001479

Experimental method

X-RAY DIFFRACTION (1.95 Å)