High-resolution structural analysis shows how Tah1 tethers Hsp90 to the R2TP complex

Area of Science:

• Molecular biology
• Structural biology
• Biochemistry

Background:

• The Hsp90 chaperone is vital for cellular processes, including snoRNP and RNA polymerase assembly.
• Hsp90 interacts with the R2TP complex, which comprises Tah1, Pih1, Rvb1, and Rvb2 proteins.
• Tah1 acts as a bridge between Hsp90 and the R2TP complex.

Purpose of the Study:

• To determine the high-resolution solution structures of Tah1, both free and bound to an Hsp90 C-terminal peptide.
• To elucidate the structural basis for Tah1-Hsp90 interaction and the role of Tah1's capping helix.
• To investigate the function of Tah1's C-terminal region in R2TP complex assembly.

Main Methods:

• High-resolution solution structure determination (NMR or X-ray crystallography).
• Biochemical assays to assess protein-protein interactions.
• Peptide-binding studies with Hsp90 C-terminal fragments.

Main Results:

• The TPR (tetratricopeptide repeat) fold of Tah1 is conserved in free and Hsp90-bound states.
• Tah1's capping helix is essential for recognizing the Hsp90 (704)EMEEVD(709) motif.
• A specific π/S-CH3 interaction occurs between Tah1 Tyr82 and Hsp90 Met705.
• The unfolded Tah1 C-terminal region is critical for recruiting the Pih1 C-terminal domain and folds upon binding.

Conclusions:

• Tah1's structure and interactions are key to bridging Hsp90 and the R2TP complex.
• The capping helix and C-terminal region of Tah1 play distinct but essential roles in Hsp90-R2TP complex formation.
• Structural insights into Tah1 function provide a basis for understanding snoRNP and RNA polymerase assembly.