Research Topics
| JOSEPH FALKESummaryAffiliation: University of Colorado Country: USA Publications
Research Grants
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Detail Information
Publications
Evidence that both ligand binding and covalent adaptation drive a two-state equilibrium in the aspartate receptor signaling complexJ A Bornhorst
Department of Chemistry and Biochemistry, University of Colorado at Boulder, Boulder, Colorado 80309-0215, USA
J Gen Physiol 118:693-710. 2001..It follows that the attractant and adaptation signals drive the same conformational change between the two settings of a toggle. An approach that quantifies the fractional occupancy of the on- and off-states is illustrated...- The two-component signaling pathway of bacterial chemotaxis: a molecular view of signal transduction by receptors, kinases, and adaptation enzymesJ J Falke
Department of Chemistry and Biochemistry, University of Colorado, Boulder 80309 0215, USA
Annu Rev Cell Dev Biol 13:457-512. 1997..Overall, the chemosensory pathway and the propulsion system it regulates provide an ideal system in which to probe molecular principles underlying complex cellular signaling and behavior... - Cooperativity between bacterial chemotaxis receptorsJoseph J Falke
Department of Chemistry and Biochemistry and Molecular Biophysics Program, University of Colorado, Boulder, CO 80309-0215, USA
Proc Natl Acad Sci U S A 99:6530-2. 2002 
Enzymology. A moving storyJoseph J Falke
Molecular Biophysics Program and The Department of Chemistry and Biochemistry, University of Colorado, Boulder, CO 80309, USA
Science 295:1480-1. 2002- Quantitative analysis of aspartate receptor signaling complex reveals that the homogeneous two-state model is inadequate: development of a heterogeneous two-state modelJoshua A Bornhorst
Department of Chemistry and Biochemistry, University of Colorado at Boulder, Boulder, CO 80309 0215, USA
J Mol Biol 326:1597-614. 2003..This method suggests that the ratio of receptor dimers to CheA dimers in the assembled complex is 6:1 or less... - Transmembrane signaling in bacterial chemoreceptorsJ J Falke
Department of Chemistry and Biochemistry, University of Colorado, 80309 0215, Boulder, CO, USA
Trends Biochem Sci 26:257-65. 2001..Multiple, independent lines of evidence indicate that, in the periplasmic and transmembrane domains, conformational signaling is a piston-type sliding of the signaling helix towards the cytoplasm... - Structure of a conserved receptor domain that regulates kinase activity: the cytoplasmic domain of bacterial taxis receptorsJ J Falke
Department of Chemistry and Biochemistry, University of Colorado, Boulder 80309 0215, USA
Curr Opin Struct Biol 10:462-9. 2000..These results represent an important step toward a mechanistic understanding of receptor-to-kinase information transfer... - Adaptation mechanism of the aspartate receptor: electrostatics of the adaptation subdomain play a key role in modulating kinase activityDiane J Starrett
Molecular Biophysics Program and Department of Chemistry and Biochemistry, University of Colorado, Boulder, Colorado 80309-0215, USA
Biochemistry 44:1550-60. 2005..Overall, this study highlights the importance of electrostatics in signal transduction and regulation of kinase activity by the cytoplasmic domain of the aspartate receptor... - Conserved glycine residues in the cytoplasmic domain of the aspartate receptor play essential roles in kinase coupling and on-off switchingMatthew D Coleman
Molecular Biophysics Program and Department of Chemistry and Biochemistry, University of Colorado, Boulder, Colorado 80309 0215, USA
Biochemistry 44:7687-95. 2005.... - Engineered socket study of signaling through a four-helix bundle: evidence for a yin-yang mechanism in the kinase control module of the aspartate receptorKalin E Swain
Department of Chemistry and Biochemistry and Molecular Biophysics Program, University of Colorado, Boulder, Colorado 80309 0215, USA
Biochemistry 48:9266-77. 2009.... - C2 domain of protein kinase C alpha: elucidation of the membrane docking surface by site-directed fluorescence and spin labelingSusy C Kohout
Department of Chemistry and Biochemistry, University of Colorado, Boulder, Colorado 80309-0215, USA
Biochemistry 42:1254-65. 2003..The data support a model in which the beta-strands are tilted toward the parallel orientation relative to the membrane surface... - CheA Kinase of bacterial chemotaxis: chemical mapping of four essential docking sitesAaron S Miller
Molecular Biophysics Program, Department of Chemistry and Biochemistry, University of Colorado, Boulder, Colorado 80309 0215, USA
Biochemistry 45:8699-711. 2006..Finally, the results provide new structural constraints allowing the development of improved models for core complex architecture... - Side chains at the membrane-water interface modulate the signaling state of a transmembrane receptorAaron S Miller
Department of Chemistry and Biochemistry, University of Colorado, Boulder, Colorado 80309-0215, USA
Biochemistry 43:1763-70. 2004.... - Ca2+ activation of the cPLA2 C2 domain: ordered binding of two Ca2+ ions with positive cooperativityNathan J Malmberg
Molecular Biophysics Program, Department of Chemistry and Biochemistry, University of Colorado, Boulder, Colorado 80301-0215, USA
Biochemistry 43:16320-8. 2004..This initial binding event prepares the conformation and protonation state of the remaining site for Ca(2+) binding, enabling the second Ca(2+) ion to bind with higher affinity than the first as required for positive cooperativity... - Mechanism of specific membrane targeting by C2 domains: localized pools of target lipids enhance Ca2+ affinityJohn A Corbin
Molecular Biophysics Program, and Department of Chemistry and Biochemistry, University of Colorado, Boulder, Colorado 80309 0215, USA
Biochemistry 46:4322-36. 2007.... - Structure of the conserved HAMP domain in an intact, membrane-bound chemoreceptor: a disulfide mapping studyKalin E Swain
Department of Chemistry and Biochemistry and Molecular Biophysics Program, University of Colorado, Boulder, Colorado 80309 0215, USA
Biochemistry 46:13684-95. 2007..A model incorporating HAMP into the full receptor structure is proposed... - C2 domains of protein kinase C isoforms alpha, beta, and gamma: activation parameters and calcium stoichiometries of the membrane-bound stateSusy C Kohout
Department of Chemistry and Biochemistry, University of Colorado, Boulder, Colorado 80309-0215, USA
Biochemistry 41:11411-24. 2002.... - Use of EPR power saturation to analyze the membrane-docking geometries of peripheral proteins: applications to C2 domainsNathan J Malmberg
Molecular Biophysics Program and Department of Chemistry and Biochemistry, University of Colorado, Boulder, Colorado 80309 0215, USA
Annu Rev Biophys Biomol Struct 34:71-90. 2005..Representative applications to Ca(2+)-activated, membrane-docking C2 domains are described... 
Effect of PIP2 binding on the membrane docking geometry of PKC alpha C2 domain: an EPR site-directed spin-labeling and relaxation studyKyle E Landgraf
Department of Chemistry and Biochemistry and the Molecular Biophysics Program, University of Colorado, Boulder, Colorado 80309 0215, USA
Biochemistry 47:8301-16. 2008..Finally, the results demonstrate that EPR relaxation methods are sufficiently sensitive to detect signaling-induced changes in the membrane docking geometries of peripheral membrane proteins...- Specific translocation of protein kinase Calpha to the plasma membrane requires both Ca2+ and PIP2 recognition by its C2 domainJohn H Evans
Molecular Biophysics Program and Department of Chemistry and Biochemistry, University of Colorado, Boulder, Boulder, CO 80309 0215, USA
Mol Biol Cell 17:56-66. 2006..Instead, targeting specificity is provided by basic residues on beta-strands 3-4, which bind to plasma membrane PIP2... - Evidence that the adaptation region of the aspartate receptor is a dynamic four-helix bundle: cysteine and disulfide scanning studiesSusanna E Winston
Department of Chemistry and Biochemistry, University of Colorado at Boulder, Boulder, Colorado 80309-0215, USA
Biochemistry 44:12655-66. 2005..A mechanistic model is proposed in which a signal is transmitted through the adaptation subdomain by a change in supercoiling of the four-helix bundle... - Mapping out regions on the surface of the aspartate receptor that are essential for kinase activationRyan S Mehan
Department of Chemistry and Biochemistry and Molecular Biophysics Program, University of Colorado, Boulder, Colorado 80309-0215, USA
Biochemistry 42:2952-9. 2003.... - Use of fluorescence resonance energy transfer to monitor Ca(2+)-triggered membrane docking of C2 domainsEric A Nalefski
Department of Chemistry and Biochemistry, University of Colorado, Boulder, CO, USA
Methods Mol Biol 172:295-303. 2002 - Single-molecule fluorescence studies of a PH domain: new insights into the membrane docking reactionJefferson D Knight
Molecular Biophysics Program, Department of Chemistry and Biochemistry, University of Colorado, Boulder, Colorado, USA
Biophys J 96:566-82. 2009..Overall, this study shows that in vitro single-molecule TIRFM provides a new window into the molecular mechanisms of membrane docking reactions... - Membrane-docking loops of the cPLA2 C2 domain: detailed structural analysis of the protein-membrane interface via site-directed spin-labelingNathan J Malmberg
Department of Chemistry and Biochemistry, University of Colorado, Boulder, Colorado 80309 0215, USA
Biochemistry 42:13227-40. 2003.... - The core signaling proteins of bacterial chemotaxis assemble to form an ultrastable complexAnnette H Erbse
Department of Chemistry, and Biochemistry and Molecular Biophysics Program, University of Colorado, Boulder, Colorado 80309 0215, USA
Biochemistry 48:6975-87. 2009..Possible biological functions of ultrastability are discussed... - GRP1 pleckstrin homology domain: activation parameters and novel search mechanism for rare target lipidJohn A Corbin
Molecular Biophysics Program and The Department of Chemistry and Biochemistry, University of Colorado, Boulder, Colorado 80309-0215, USA
Biochemistry 43:16161-73. 2004.... - Molecular mechanism of an oncogenic mutation that alters membrane targeting: Glu17Lys modifies the PIP lipid specificity of the AKT1 PH domainKyle E Landgraf
Department of Chemistry and Biochemistry and Molecular Biophysics Program, University of Colorado, Boulder, Colorado 80309 0215, USA
Biochemistry 47:12260-9. 2008..Moreover, the findings strongly implicate the native Glu17 side chain as a key element of PIP lipid specificity in the wild-type AKT1 PH domain. Other PH domains may employ an analogous anionic residue to control PIP specificity... - Thermal domain motions of CheA kinase in solution: Disulfide trapping reveals the motional constraints leading to trans-autophosphorylationSusan L Gloor
Department of Chemistry and Biochemistry, University of Colorado, Boulder, 80309 0215, USA
Biochemistry 48:3631-44. 2009..Finally, a working model is proposed for the motional constraints that limit the P1 domain to the region of space near the P4' catalytic domain of the sister subunit... - Cation charge and size selectivity of the C2 domain of cytosolic phospholipase A(2)Eric A Nalefski
Department of Chemistry and Biochemistry, University of Colorado at Boulder, Boulder, Colorado 80309-0215, USA
Biochemistry 41:1109-22. 2002..These features are proposed to stem from the unique structural features of the metal ion-binding site in the C2 domain... - Ca2+ influx is an essential component of the positive-feedback loop that maintains leading-edge structure and activity in macrophagesJohn H Evans
Department of Chemistry and Biochemistry, University of Colorado, Boulder, CO 80309 0215, USA
Proc Natl Acad Sci U S A 104:16176-81. 2007..These findings support the working hypothesis that a local, leading-edge Ca(2+) signal recruits PKCalpha as a central player in the positive-feedback loop... - Chemotaxis receptors and signalingAaron F Miller
Department of Chemistry and Biochemistry, University of Colorado, Boulder, Colorado 80309, USA
Adv Protein Chem 68:393-444. 2004..Extensive mutagenesis studies have been carried out, and have begun to identify critical residues involved in ligand binding, receptor activation, and transmembrane signaling... - Bacterial chemoreceptors: high-performance signaling in networked arraysGerald L Hazelbauer
Department of Biochemistry, University of Missouri Columbia, Columbia, MO 65211, USA
Trends Biochem Sci 33:9-19. 2008..These new data suggest multiple levels of molecular interactions, each of which contribute specific functional features and together create a sophisticated signaling device... - Chemotaxis receptor complexes: from signaling to assemblyRobert G Endres
Department of Molecular Biology, Princeton University, Princeton, New Jersey, United States of America
PLoS Comput Biol 3:e150. 2007..We propose that the kinetics of complex assembly can be measured in vitro from the temporal response to a perturbation of the complex free energies, e.g., by addition of ligand... - Use of site-directed cysteine and disulfide chemistry to probe protein structure and dynamics: applications to soluble and transmembrane receptors of bacterial chemotaxisRandal B Bass
Analytical Sciences, Amgen Inc, Seattle, WA, USA
Methods Enzymol 423:25-51. 2007..This chapter details these methods and illustrates applications to two proteins from the bacterial chemotaxis pathway: the periplasmic galactose binding protein and the transmembrane aspartate receptor... - The PICM chemical scanning method for identifying domain-domain and protein-protein interfaces: applications to the core signaling complex of E. coli chemotaxisRandal B Bass
Analytical Sciences, Amgen Inc, Seattle, WA, USA
Methods Enzymol 423:3-24. 2007.... - Membrane orientation and position of the C2 domain from cPLA2 by site-directed spin labelingApril A Frazier
Department of Chemistry and Biophysics Program, University of Virginia, Charlottesville, Virginia 22904-4319, USA
Biochemistry 41:6282-92. 2002..Upon membrane docking, spin labels in the Ca(2+)-binding loops exhibit decreases in local motion, suggesting either changes in tertiary contacts due to protein conformational changes and/or interactions with lipid... - Self-induced docking site of a deeply embedded peripheral membrane proteinSimon Jaud
Department of Chemistry, and Department of Physiology and Biophysics, University of California, Irvine, California, USA
Biophys J 92:517-24. 2007....
Research Grants
- Calcium Activated Membrane Targeting by the C2 DomainJOSEPH FALKE; Fiscal Year: 2004..Furthermore, comparative studies of C2 domains will provide information crucial to genomic analyses of many signaling pathways. ..
- Activation and Dynamics of Receptors and KinasesJOSEPH FALKE; Fiscal Year: 2005..Overall, the broad goal of these studies is to understand the mechanisms of transmembrane signaling, receptor adaptation, and kinase regulation in a fully assembled, multi-protein signaling complex. ..
- Activation and Dynamics of Receptors and KinasesJOSEPH FALKE; Fiscal Year: 2007..Overall, the broad goal of these studies is to understand the mechanisms of receptor transmembrane signaling, receptor adaptation, and kinase regulation in the native environment that includes the membrane and other pathway components. ..
- Mechanisms of Membrane Targeting by C2 and PH DomainsJOSEPH FALKE; Fiscal Year: 2007..Overall, the results of the proposed studies will have significant implications for a molecular understanding of C2 and PH domain signaling in human health and disease. ..
- Predoctoral Training Molecular BiophysicsJOSEPH FALKE; Fiscal Year: 2007....
- Activation and Dynamics of Receptors and KinasesJOSEPH FALKE; Fiscal Year: 2009..abstract_text> ..
- Mechanisms of Regulated Membrane TargetingJOSEPH FALKE; Fiscal Year: 2009..Preliminary results reveal that the E17K mutation enhances membrane targeting by changing the target lipid specificity of the PH domain, thereby defining the molecular mechanism of this important oncogenic mutation. ..
- Mechanisms of Regulated Membrane TargetingJoseph J Falke; Fiscal Year: 2010..Preliminary results reveal that the E17K mutation enhances membrane targeting by changing the target lipid specificity of the PH domain, thereby defining the molecular mechanism of this important oncogenic mutation. ..
- Membrane Proteins - Structure and MechanismJOSEPH FALKE; Fiscal Year: 2002..Overall, the conference will provide a forum in which membrane protein researchers come together to present exciting new results with broad, significant implications for membrane protein structure and mechanism. ..
- RECEPTORS & SIGNALING PROTEINS--DYNAMICS & ACTIVATIONJOSEPH FALKE; Fiscal Year: 1993..In addition, the E. coli components exhibit interesting parallels with certain eukaryotic receptors and signaling proteins, such as the insulin receptor and H-ras, respectively...
- BIOPHYSICAL STUDIES OF PROTEIN STRUCTURE AND DYNAMICSJOSEPH FALKE; Fiscal Year: 1992..In addition, bacterial binding proteins have been useful as detectors in assays for genetic diseases and treatment (reviewed in ref. 39)...
- ACTIVATION & DYNAMICS OF RECEPTORS & SIGNALING PROTEINSJOSEPH FALKE; Fiscal Year: 2000..19F NMR and other solution methods will probe the effects of phosphorylation on both the conformation and dynamics of the activation loop that directly controls kinase activity. ..
- Activation and Dynamics of Receptors and KinasesJoseph J Falke; Fiscal Year: 2010..Moreover, it is the first signaling circuit found to be ultrastable, providing a platform for understanding ultrastability and for designing new ultrastable biosensors. ..