Conservation of transition state structure in fast folding peripheral subunit-binding domains

Sharpe, Timothy D. and Ferguson, Neil and Johnson, Christopher M. and Fersht, Alan R.. (2008) Conservation of transition state structure in fast folding peripheral subunit-binding domains. Journal of Molecular Biology, 383 (1). pp. 224-237.

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Official URL: http://edoc.unibas.ch/47496/

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Phi-value analysis was used to characterise the structure of the transition state (TS) for folding of POB L146A Y166W, a peripheral subunit-binding domain that folds in microseconds. Helix 2 was structured in the TS with consolidating interactions from the structured loop that connects the two alpha-helices. This distribution of Phi-values was very similar to that determined for E3BD F166W, a homologue with high sequence and structural similarity. The extrapolated folding rate constants in water at 298 K were 210,000 s(-1) for POB and 27,500 s(-1) for E3BD. A contribution to the faster folding of POB came from its having significantly greater helical propensity in helix 2, the folding nucleus. The folding rate also appeared to be influenced by differences in the sequence and structural properties of the loop connecting the two helices. Unimodal downhill folding has been proposed as a conserved, biologically important property of peripheral subunit-binding domains. POB folds five times faster and E3BD folds slower than a proposed limit of 40,000 s(-1) for barrier-limited folding. However, experimental evidence strongly suggests that both POB L146A Y166W and E3BD F166W fold in a barrier-limited process through a very similar TS ensemble.
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Services Biozentrum > Biophysics Facility (Sharpe)
UniBasel Contributors:Sharpe, Timothy
Item Type:Article, refereed
Article Subtype:Research Article
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:29 Nov 2017 07:27
Deposited On:29 Nov 2017 07:27

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