Abstract：
: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.
journal_name
J Mol Bioljournal_title
Journal of molecular biologyauthors
Sharpe TD,Ferguson N,Johnson CM,Fersht ARdoi
10.1016/j.jmb.2008.06.081subject
Has Abstractpub_date
2008-10-31 00:00:00pages
224-37issue
1eissn
0022-2836issn
1089-8638pii
S0022-2836(08)00808-5journal_volume
383pub_type
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