Shilpi Goel

Date of Award


Degree Type


Degree Name

Master of Science




Dr. Priti Krishna


The highly conserved and abundant cystosolic molecular chaperone Hsp90 plays a key role in signal transduction networks, cell-cycle control, protein degradation and protein trafficking. Two key features regarding the mechanism of Hsp90 action are: 1) Hsp90 operates as part of a multichaperone complex, facilitating the folding of the client proteins into their stable or activatable conformations, and 2) Hsp90 functions are driven by the hydrolysis of ATP. The functional cycle of Hsp90 requires a cohort of co­ chaperones that regulate the ATPase activity of Hsp90 and confer specificity to its interaction with client proteins. Several Hsp90 co-chaperones contain the tetratricopeptide repeat (TPR) domain, which is a degenerate 34-amino acid sequence found in multiple copies in proteins. The TPR domain containing co-chaperones of Hsp90 interact with the highly conserved EEVD motif present at the C-terminal end of Hsp90. The interaction occurs via a subset of basic residues in the TPR domain that form a ‘carboxylate clamp’ and interact with the acidic side chains of the EEVD motif. These basic amino acid positions are conserved in the TPR domains of known Hsp90 co­ chaperones. An in silico search for TPR proteins in Arabidopsis, followed by identification of at least one three-motif TPR domain and the presence of conserved basic residues within these motifs, identified 23 proteins as potential Hsp90 interactors. Of these, 11 proteins are newly identified. Based on the expression patterns of the various TPR proteins and Hsp90, AT4G22670 is hypothesized as a major general co-chaperone of Hsp90 under normal growing conditions and heat stress conditions. Preliminary phylogenetic analyses were carried out for AtTPR2 (AT1G04130), which indicated an important role for this protein in eukaryotes. Orthologs of most of the known Hsp90 co­ chaperones were identified in Arabidopsis on the basis of sequence comparisons, but the possible absence of Cdc37 in plants raises the question of how the protein kinase clientale of Hsp90 is chaperoned in plants. These results indicate that while the Hsp90 co­ chaperone network is mostly conserved in plants, it has evolved some unique features, and that Hsp90 relies on TPR domain containing co-chaperones much more than it was previously realized



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