ArticleThe Journal of biological chemistry1995
Lock on/off disulfides identify the transmembrane signaling helix of the aspartate receptor.
Article in The Journal of biological chemistry, 1995. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.
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Who cites it
55 citing papers in PubMed, 130 citations in OpenAlex.
- Mechanism of metal ion-induced activation of a two-component sensor kinase.The Biochemical journal · 2019Article
- Evidence for a Helix-Clutch Mechanism of Transmembrane Signaling in a Bacterial Chemoreceptor.Journal of molecular biology · 2016Article
- Increasing and decreasing the ultrastability of bacterial chemotaxis core signaling complexes by modifying protein-protein contacts.Biochemistry · 2014Article
- Cys-scanning disulfide crosslinking and bayesian modeling probe the transmembrane signaling mechanism of the histidine kinase, PhoQ.Structure (London, England : 1993) · 2014Article
- New insights into bacterial chemoreceptor array structure and assembly from electron cryotomography.Biochemistry · 2014Article
- Article
- Discovery of novel chemoeffectors and rational design of Escherichia coli chemoreceptor specificity.Proceedings of the National Academy of Sciences of the United States of America · 2013Article
- In vivo studies suggest that induction of VanS-dependent vancomycin resistance requires binding of the drug to D-Ala-D-Ala termini in the peptidoglycan cell wall.Antimicrobial agents and chemotherapy · 2013Article
- Molecular architecture of chemoreceptor arrays revealed by cryoelectron tomography of Escherichia coli minicells.Proceedings of the National Academy of Sciences of the United States of America · 2012Article
- Identifying functionally important conformational changes in proteins: activation of the yeast α-factor receptor Ste2p.Journal of molecular biology · 2012Article
- The S helix mediates signal transmission as a HAMP domain coiled-coil extension in the NarX nitrate sensor from Escherichia coli K-12.Journal of bacteriology · 2010Article
- Phototactic and chemotactic signal transduction by transmembrane receptors and transducers in microorganisms.Sensors (Basel, Switzerland) · 2010Review
- Conserved polar residues stabilize transmembrane domains and promote oligomerization in human nucleoside triphosphate diphosphohydrolase 3.Biochemistry · 2009Article
- Engineered socket study of signaling through a four-helix bundle: evidence for a yin-yang mechanism in the kinase control module of the aspartate receptor.Biochemistry · 2009Article
- The core signaling proteins of bacterial chemotaxis assemble to form an ultrastable complex.Biochemistry · 2009Article
- Structure-function relationships in the HAMP and proximal signaling domains of the aerotaxis receptor Aer.Journal of bacteriology · 2008Article
- Structure of the conserved HAMP domain in an intact, membrane-bound chemoreceptor: a disulfide mapping study.Biochemistry · 2007Article
- Use of site-directed cysteine and disulfide chemistry to probe protein structure and dynamics: applications to soluble and transmembrane receptors of bacterial chemotaxis.Methods in enzymology · 2007Article
- Evidence that the adaptation region of the aspartate receptor is a dynamic four-helix bundle: cysteine and disulfide scanning studies.Biochemistry · 2005Article
- Role of predicted transmembrane domains for type III translocation, pore formation, and signaling by the Yersinia pseudotuberculosis YopB protein.Infection and immunity · 2005Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
The aspartate receptor of the bacterial chemotaxis pathway regulates the autophosphorylation rate of a cytoplasmic histidine kinase in response to ligand binding. The transmembrane signal, which is transmitted from the periplasmic aspartate-binding domain to the cytoplasmic regulatory domain, is carried by an intramolecular conformational change within the homodimeric receptor structure. The present work uses engineered cysteines and disulfide bonds to probe the nature of this conformational change, focusing in particular on the role of the second transmembrane alpha-helix. Altogether 26 modifications, consisting of 13 cysteine pairs and the corresponding disulfide bonds, have been introduced into the contacts between the second transmembrane helix and adjacent helices. The effects of these modifications on the transmembrane signal have been quantified by in vitro assays which measure (i) ligand binding, (ii) receptor-mediated regulation of kinase activity, and (iii) receptor methylation. All three parameters are observed to be highly sensitive to perturbations of the second transmembrane helix. In particular, 13 of the 26 modifications (6 cysteine pairs and 7 disulfides) significantly increase or decrease aspartate affinity, while 15 of the 26 modifications (6 cysteine pairs and 10 disulfides) destroy transmembrane kinase regulation. Importantly, 3 of the perturbing disulfides are found to lock the receptor in the "on" or "off" signaling state by covalently constraining the second transmembrane helix, demonstrating that it is possible to use engineered disulfides to lock the signaling function of a receptor protein. A separate aspect of the study probes the thermal motions of the second transmembrane helix: 4 disulfides designed to trap large amplitude twisting motions are observed to disrupt function but form readily, suggesting that the helix is mobile. Together the results support a model in which the second transmembrane helix is a mobile signaling element responsible for communicating the transmembrane signal.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.