Different mechanistic requirements for prokaryotic and eukaryotic chaperonins: A lattice study

Etai Jacob, Amnon Horovitz, Ron Unger

Research output: Contribution to journalArticlepeer-review

24 Scopus citations


Motivation: The folding of many proteins in vivo and in vitro is assisted by molecular chaperones. A well-characterized molecular chaperone system is the chaperonin GroEL/GroES from Escherichia coli which has a homolog found in the eukaryotic cytosol called CCT. All chaperonins have a ring structure with a cavity in which the substrate protein folds. An interesting difference between prokaryotic and eukaryotic chaperonins is in the nature of the ATP-mediated conformational changes that their ring structures undergo during their reaction cycle. Prokaryotic chaperonins are known to exhibit a highly cooperative concerted change of their cavity surface while in eukaryotic chaperonins the change is sequential. Approximately 70% of proteins in eukaryotic cells are multi-domain whereas in prokaryotes single-domain proteins are more common. Thus, it was suggested that the different modes of action of prokaryotic and eukaryotic chaperonins can be explained by the need of eukaryotic chaperonins to facilitate folding of multi-domain proteins. Results: Using a 2D square lattice model, we generated two large populations of single-domain and double-domain substrate proteins. Chaperonins were modeled as static structures with a cavity wall with which the substrate protein interacts. We simulated both concerted and sequential changes of the cavity surfaces and demonstrated that folding of single-domain proteins benefits from concerted but not sequential changes whereas double-domain proteins benefit also from sequential changes. Thus, our results support the suggestion that the different modes of allosteric switching of prokaryotic and eukaryotic chaperonin rings have functional implications as it enables eukaryotic chaperonins to better assist multi-domain protein folding.

Original languageEnglish
Pages (from-to)i240-i248
Issue number13
StatePublished - 1 Jul 2007

Bibliographical note

Funding Information:
We thank Inna Myslyuk for assistance with the artwork and Ehud Schreiber for the useful comments. The computations in this research were performed on the EGEE grid and we thank Assaf Gottlieb for technical support. This work was supported by Israel Science Foundation grant (67/05) to A.H.


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