2lsv | pdb_00002lsv
The NMR high resolution structure of yeast Tah1 in complex with the Hsp90 C-terminal tail
Structural highlights
Function[HSP82_YEAST] Molecular chaperone that promotes the maturation, structural maintenance and proper regulation of specific target proteins involved in cell cycle control and signal transduction. Undergoes a functional cycle that is linked to its ATPase activity. The nucleotide-free form of the dimer is found in an open conformation in which the N-termini are not dimerized and the complex is ready for client protein binding. Binding of ATP induces large conformational changes, resulting in the formation of a ring-like closed structure in which the N-terminal domains associate intramolecularly with the middle domain and also dimerize with each other, stimulating their intrinsic ATPase activity and acting as a clamp on the substrate. Finally, ATP hydrolysis results in the release of the substrate. This cycle probably induces conformational changes in the client proteins, thereby causing their activation. Interacts dynamically with various co-chaperones that modulate its substrate recognition, ATPase cycle and chaperone function. Required for growth at high temperatures.[1] Publication Abstract from PubMedThe ubiquitous Hsp90 chaperone participates in snoRNP and RNA polymerase assembly through interaction with the R2TP complex. This complex includes the proteins Tah1, Pih1, Rvb1, and Rvb2. Tah1 bridges Hsp90 to R2TP. Its minimal TPR domain includes two TPR motifs and a capping helix. We established the high-resolution solution structures of Tah1 free and in complex with the Hsp90 C-terminal peptide. The TPR fold is similar in the free and bound forms and we show experimentally that in addition to its solvating/stabilizing role, the capping helix is essential for the recognition of the Hsp90 704EMEEVD709 motif. In addition to Lys79 and Arg83 from the carboxylate clamp, this helix bears Tyr82 forming a pi/S-CH3 interaction with Hsp90 M705 from the peptide 310 helix. The Tah1 C-terminal region is unfolded, and we demonstrate that it is essential for the recruitment of the Pih1 C-terminal domain and folds upon binding. High-Resolution Structural Analysis Shows How Tah1 Tethers Hsp90 to the R2TP Complex.,Back R, Dominguez C, Rothe B, Bobo C, Beaufils C, Morera S, Meyer P, Charpentier B, Branlant C, Allain FH, Manival X Structure. 2013 Sep 4. pii: S0969-2126(13)00296-7. doi:, 10.1016/j.str.2013.07.024. PMID:24012479[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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