A5009360938- Heat shock proteins research
- Fungal and yeast genetics research
- thermodynamics and calorimetric analyses
- RNA and protein synthesis mechanisms
- Protein Structure and Dynamics
- RNA modifications and cancer
- RNA Research and Splicing
- Enzyme Structure and Function
- Endoplasmic Reticulum Stress and Disease
- Genetics, Aging, and Longevity in Model Organisms
- Fermentation and Sensory Analysis
- Viral Infectious Diseases and Gene Expression in Insects
- ATP Synthase and ATPases Research
- Microbial Metabolic Engineering and Bioproduction
- Biofuel production and bioconversion
- Computational Drug Discovery Methods
- DNA Repair Mechanisms
- Photosynthetic Processes and Mechanisms
- Amino Acid Enzymes and Metabolism
- Mitochondrial Function and Pathology
- Toxin Mechanisms and Immunotoxins
- Genomics, phytochemicals, and oxidative stress
- Polyamine Metabolism and Applications
- Insect and Pesticide Research
- Plant biochemistry and biosynthesis
University of Sheffield
2009-2023
Universitätsklinikum Tübingen
2012
Addenbrooke's Hospital
2012
University of Cambridge
1974-2012
Institute of Cancer Research
2006
University College London
1995-2004
Aarhus University
1975-1982
University of Washington
1981
The Honourable Society of Lincoln's Inn
1976-1979
MRC Laboratory of Molecular Biology
1973-1975
The cellular activity of several regulatory and signal transduction proteins, which depend on the Hsp90 molecular chaperone for folding, is markedly decreased by geldanamycin radicicol (monorden). We now show that these unrelated compounds both bind to N-terminal ATP/ADP-binding domain Hsp90, with displaying nanomolar affinity, inhibit inherent ATPase essential its function in vivo. Crystal structure determinations complexes identify key aspects their nucleotide mimicry suggest a rational...
<i>In vivo</i> activation of client proteins by Hsp90 depends on its ATPase-coupled conformational cycle and interaction with a variety co-chaperone proteins. For some the Sti1/Hop/p60 acts as "scaffold," recruiting Hsp70 bound to early in suppressing ATP turnover during loading phase. Recruitment protein kinase clients complex appears involve specialized co-chaperone, Cdc37p/p50<sup>cdc37</sup>, whose binding is mutually exclusive Sti1/Hop/p60. We now show that like Sti1/Hop/p60, also...
Aquaporins and aquaglyceroporins form the membrane channels that mediate fluxes of water small solute molecules into out cells. Eukaryotes often use mitogen-activated protein kinase (MAPK) cascades for intracellular signaling stress. This study reveals an aquaglyceroporin being destabilized by direct MAPK phosphorylation also a stress resistance acquired through this channel loss. Hog1 is transiently activated in yeast exposed to high, toxic levels acetic acid. then phosphorylates plasma...
ATP hydrolysis by the Hsp90 molecular chaperone requires a connected set of conformational switches triggered binding to N-terminal domain in dimer. Central this is segment structure, which closes like "lid" over bound ATP, promoting dimerization and assembly competent active site. mutants that influence these have strong effects on ATPase activity. activity specifically regulated co-chaperones, directly switches. Here we analyzed effect mutations (using isothermal titration calorimetry...
Activation of protein kinase clients by the Hsp90 system is mediated cochaperone Cdc37. Cdc37 requires phosphorylation at Ser13, but little known about regulation this essential posttranslational modification. We show that Ser13 uncomplexed phosphorylated in vivo, as well binary complex with a (C-K), or ternary and (H-C-K). Whereas pSer13-Cdc37 H-C-K resistant to nonspecific phosphatases, it efficiently dephosphorylated chaperone-targeted phosphatase 5 (PP5/Ppt1), which does not affect...
ABSTRACT The Hsp90 chaperone cycle catalyzes the final activation step of several important eukaryotic proteins (Hsp90 “clients”). Although largely a functional form Hsp90, an Hsp90-Gal4p DNA binding domain fusion (Hsp90-BD) displays no strong interactions in yeast two-hybrid system, consistent with general transience most Hsp90-client associations. Strong vivo are though detected when E33A mutation is introduced into this bait, that should arrest complexes at stage where client stabilized,...
ABSTRACT Growth of Saccharomyces cerevisiae in the presence weak-acid preservative sorbic acid results induction ATP-binding cassette (ABC) transporter Pdr12 plasma membrane (P. Piper, Y. Mahe, S. Thompson, R. Pandjaitan, C. Holyoak, Egner, M. Muhlbauer, P. Coote, and K. Kuchler, EMBO J. 17:4257–4265, 1998). appears to mediate resistance water-soluble, monocarboxylic acids with chain lengths from C 1 7 . Exposure aliphatic greater than resulted no observable sensitivity Δpdr12 mutant cells...
Weak organic acids such as sorbate are potent fungistatic agents used in food preservation, but their intracellular targets poorly understood. We thus searched for potential target genes and signaling components the yeast genome using contemporary genome-wide functional assays well DNA microarray profiling. Phenotypic screening of EUROSCARF collection revealed existence numerous sorbate-sensitive strains. Sorbate hypersensitivity was detected mutants shikimate biosynthesis pathway, strains...