The Jakob Lab
Ursula Jakob, Ph.D.
Genomic sequencing projects have generated a new challenge: to elucidate the function of newly discovered genes. Our lab is focusing on the function and 3-dimensional structure of recently identified heat shock protein families.
All organisms respond to sudden temperature increase, oxygen radicals or viral infections by the overexpression of a defined set of conserved heat shock proteins (Hsps). The induction of these proteins is triggered by the accumulation of improperly folded proteins in the cell. These protein folding intermediates have a high tendency to aggregate irreversibly, a phenomena that can lead to lethal consequences for cells and organisms.
By applying structural, functional and genetic tools, we have recently succeeded in determining the function and high resolution three-dimensional structure of two new, highly conserved heat shock proteins: i) Hsp33, a redox regulated molecular chaperone that appears to be specialized to protect cells and organisms against oxidative stress and ii) RrmJ (FtsJ), the first rRNA methyltransferase under heat shock control. Deletion of rrmJ, leads to the premature dissociation of intact 70S ribosomes causing severe growth defects under all temperatures tested.
We are using proteomics and microarray technology to identify other redox regulated proteins and to study the consequences of heat and oxidative stress on cells and organisms. This work will enhance our understanding about the impact of oxidative stress on the heat shock response as well as about the role RNA modification plays during the cellular response of stress treatment.
Global Methods to Monitor the Thiol-Disulfide State of Proteins in vivo
XIAP Is a copper binding protein deregulated in Wilson's disease and other copper toxicosis disorders.
CoSMoS: Conserved Sequence Motif Search in the proteome.
Severe Oxidative Stress Causes Inactivation of DnaK and Activation of the Redox-Regulated Chaperone Hsp33.
Beyond transcription-new mechanisms for the regulation of molecular chaperones.
Protein Thiol Modifications Visualized In Vivo.
The Crystal Structure of the Reduced Zn2+-Bound Form of the B. subtilis Hsp33 Chaperone and its Implications for the Activation Mechanism.
Substrate binding analysis of the 23S rRNA methyltransferase RrmJ.
Redox regulation of chaperones.
The zinc-dependent redox switch domain of the chaperone Hsp33 has a novel fold.
Activation of the redox regulated chaperone Hsp33 by domain unfolding.
Identification of a redox regulated chaperone network.
Thioredoxin 2, an oxidative stress induced protein, contains a high affinity zinc binding site.
The roles of the two zinc binding sites in DnaJ.
Not every disulfide lasts forever: disulfide bond formation as a redox switch.
Active site in RrmJ, a heat shock induced methyltransferase.
Redox regulated molecular chaperones.
The 2.2 Å Crystal Structure of Hsp33: A Heat Shock Protein with Redox-regulated Chaperone Activity.
Activation of the Redox Regulated Molecular Chaperone Hsp33-A Two Step Mechanism.
Mass Spectrometry Unravels Disulfide Bond Formation as Mechanism to Activate a Molecular Chaperone.
DsbG, a Protein Disulfide Isomerase With Chaperone Activity.
Hsp33's Redox Switch has a Novel Zinc-Binding Motif.
RNA Methylation under Heat Shock Control.
Chaperone Activity with a Redox Switch.