Javaid Yousuf Bhat,
Ph. D: Jawaharlal Nehru Centre for Advanced Scientific Research, Bangalore, India
Postdoctoral fellowship: Max Planck Institute of Biochemistry, Munich, Germany
Understanding the molecular mechanisms of the remodeling chaperone machinery
All newly synthesized proteins have to be folded into a 3D conformation for any cellular function, followed by a necessity in many essential protein complexes for a temporary assistance in assembly, maintenance or remodeling by accessory proteins called chaperones. The AAA+ (ATPases Associated with diverse cellular Activities) protein family forms one such functionally diverse, evolutionary and structurally-related energy-dependent chaperones that couple the chemical energy of ATP to the conformational remodeling of a diverse set of substrates. AAA+ proteins are present in all organisms from archaea to animals and are indispensable for cellular processes like immunity, DNA replication, protein homeostasis, stress response, organelle biogenesis, ribosome assembly, membrane integrity and vesicular transport. Accordingly, the altered or mutated versions of these chaperones have been implicated in many human diseases like cancer and neurodegeneration. Understanding the molecular principles of how these chaperones modulate their substrates may provide avenues for pharmacological interventions in the related pathologies. An integrated methodological approach of biochemistry, biophysics, structural proteomics (e.g, hydrogen deuterium exchange and chemical crosslinking coupled to mass spectrometry, native mass spectrometry and Cryo-EM) and in vivo assays will be employed.
1. Plant RuBisCo assembly in E. coli with five chloroplast chaperones including BSD2. Aigner H, Wilson RH, Bracher A, Calisse L, Bhat JY, Hartl FU, Hayer-Hartl M. Science. 2017 (PMID: 29217567).
2. Mechanism of enzyme repair by the AAA+ chaperone Rubisco activase. Bhat JY, Miličić G, Thieulin- Pardo G, Bracher A, Maxwell A, Ciniawsky S, Mueller-Cajar O, Engen JR, Hartl FU, Wendler P, Hayer- Hartl M. Molecular Cell. 2017 (PMID: 28803776).
3. Rubisco activases: AAA+ chaperones adapted to enzyme repair. Bhat JY, Thieulin-Pardo G, Hartl FU, Hayer-Hartl M. Front Mol Biosci. 2017 (PMID: 28443288).
4. Structure and mechanism of the Rubisco-assembly chaperone Raf1. Hauser T, Bhat JY, Miličić G, Wendler P, Hartl FU, Bracher A, Hayer-Hartl M. Nat Struct Mol Biol. 2015 (PMID: 26237510).
5. Substrate-induced conformational changes in Plasmodium falciparum guanosine monophosphate synthetase. Bhat JY, Venkatachala R, Balaram H. FEBS J. (PMID: 21827625).
6. Ammonia channeling in Plasmodium falciparum GMP synthetase: investigation by NMR spectroscopy and biochemical assays. Bhat JY, Venkatachala R, Singh K, Gupta K, Sarma SP, Balaram H.Biochemistry. 2011 (PMID: 21413787).