A5056532113- Heat shock proteins research
- Protein Structure and Dynamics
- Enzyme Structure and Function
- Computational Drug Discovery Methods
- Toxin Mechanisms and Immunotoxins
- Endoplasmic Reticulum Stress and Disease
- thermodynamics and calorimetric analyses
- Connexins and lens biology
- RNA and protein synthesis mechanisms
- Plant biochemistry and biosynthesis
- ATP Synthase and ATPases Research
- Genetic Neurodegenerative Diseases
- RNA Research and Splicing
Technical University of Munich
2018-2022
Center for Integrated Protein Science Munich
2018-2022
Indian Institute of Technology Delhi
2013
Hsp90 is a molecular chaperone that interacts with specific set of client proteins and assists their folding. The underlying mechanisms, involving dynamic transitions between open closed conformations, are still enigmatic. Combining nuclear magnetic resonance, small-angle x-ray scattering, biochemical experiments, we have identified key intermediate state induced by adenosine triphosphate (ATP) binding, in which rotation the N-terminal domain (NTD) yields arrangement poised for closing. This...
In the eukaryotic cytosol, Hsp70 and Hsp90 chaperone machines work in tandem with maturation of a diverse array client proteins. The transfer nonnative clients between these systems is essential to chaperoning process, but how it regulated still not clear. We discovered that NudC an factor unprecedented mode action: interacts Hsp40 Hsp40-Hsp70-client complexes displaces Hsp70. Then, interaction allows direct Hsp40-bound for further processing. Consistent this mechanism, increases activation...
The glucocorticoid receptor (GR) is an important transcription factor and drug target linked to a variety of biological functions diseases. It one the most stringent physiological clients Hsp90/Hsp70/Hsp40 chaperone system. In this study, we used single-molecule force spectroscopy by optical tweezers observe interaction GR’s ligand-binding domain (GR-LBD) with Hsp70/Hsp40 system (Hsp70/40). We show in real time that Hsp70/40 can unfold complete GR-LBD stepwise manner. Each unfolding step...
Despite their prevalence in biological systems, information about the folding pathways of large and multidomain proteins is meager, as they often unfold irreversibly under vitro conditions which make studies difficult or even impossible. The mechanism a (82 kDa) protein Malate synthase G (MSG) has been demonstrated present study using intrinsic tryptophan fluorescence, enzymatic activity, extrinsic fluorophore ANS probes for monitoring refolding process. Refolding MSG found to occur three...
Abstract Human and mouse genetic studies have demonstrated a role for DNA mismatch repair (MMR) molecular machines in modulating the rate of somatic expansion huntingtin ( HTT) CAG repeats, onset progression Huntington’s Disease (HD). MutSβ, key component MMR pathway, is heterodimeric protein MSH2 MSH3 that recognizes initiates extrahelical extrusions. Loss-of-function Msh3 reduced-expression alleles human lead to slower rates delayed disease humans, signifying as promising therapeutic...