Abstract
Chaperones, a group of proteins that assist the folding of other proteins, seem to work in a coordinated manner. Two major chaperone families are heat-shock protein families Hsp60 and Hsp70. Here we show for the first time the formation of a stable complex between chaperonin-containing TCP-1 (CCT) and Hsc70, two eukaryotic representatives of these chaperone families. This interaction takes place between the apical domain of the CCTβ subunit and the nucleotide binding domain of Hsc70, and may serve to deliver the unfolded substrate from Hsc70 to the substrate binding region of CCT. We also show that a similar interaction does not occur between their prokaryotic counterparts GroEL and DnaK, suggesting that in eukarya the two types of chaperones have evolved to a concerted action that makes the folding task more efficient.
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Acknowledgements
We thank C. Rodríguez for technical assistance and the Barcelona Supercomputing Center, Centro Nacional de Supercomputación, for providing computer resources. This work was supported by grants CSD2006-00023, BFU2007-62382/BMC and GEN2003-20642-C09-06 from the Spanish Ministry of Education (J.M.V.) and BFU2007-64452 (A.M.). This work was also funded by the EU-grant '3D repertoire' (LSHG-CT-2005-512028) and by the grant RGP63/2004 from the Human Frontiers Scientific Program.
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J.C. purified proteins and did part of the EM and image processing; J.M.-B. did part of the image processing and the docking analysis; S.H.W.S. did part of the image processing; R.S. generated several Hsc70 mutants; F.M. and A.M. generated several DnaK mutants; E.L.-V. and P.G.-P. did the homology analysis and designed some experiments; J.L.C. did part of the electron microscopy and designed some experiments; J.M.V. did the cryo-EM and devised some experiments.
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Cuéllar, J., Martín-Benito, J., Scheres, S. et al. The structure of CCT–Hsc70NBD suggests a mechanism for Hsp70 delivery of substrates to the chaperonin. Nat Struct Mol Biol 15, 858–864 (2008). https://doi.org/10.1038/nsmb.1464
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DOI: https://doi.org/10.1038/nsmb.1464
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