The energy landscape of a fast-folding protein mapped by Ala-->Gly substitutions.


A moderately stable protein with typical folding kinetics unfolds and refolds many times during its cellular lifetime. In monomeric lambda repressor this process is extremely rapid, with an average folded state lifetime of only 30 milliseconds. A thermostable variant of this protein (G46A/G48A) unfolds with the wild-type rate, but it folds in approximately 20 microseconds making it the fastest-folding protein yet observed. The effects of alanine to glycine substitutions on the folding and unfolding rate constants of the G46A/G48A variant, measured by dynamic NMR spectroscopy, indicate that the transition state is an ensemble comprised of a disperse range of conformations. This structural diversity in the transition state is consistent with the idea that folding chains are directed towards the native state by a smooth funnel-like conformational energy landscape. The kinetic data for the folding of monomeric lambda repressor can be understood by merging the new energy landscape view of folding with traditional models. This hybrid model incorporates the conformational diversity of denatured and transition state ensembles, a transition state activation energy, and the importance of intrinsic helical stabilities. Study holds ProTherm entries: 3603, 3604, 3605, 3606, 3607, 3608, 3609, 3610, 3611 Extra Details: measurements were made in the presence of 2M urea lambda repressor; energy landscape; folding kinetics;,hybrid model; alanine; glycine; transition state

Submission Details

ID: AaFopLr64

Submitter: Connie Wang

Submission Date: April 24, 2018, 8:22 p.m.

Version: 1

Publication Details
Burton RE;Huang GS;Daugherty MA;Calderone TL;Oas TG,Nat. Struct. Biol. (1997) The energy landscape of a fast-folding protein mapped by Ala-->Gly substitutions. PMID:9095199
Additional Information

Structure view and single mutant data analysis

Study data

No weblogo for data of varying length.
Colors: D E R H K S T N Q A V I L M F Y W C G P

Data Distribution

Studies with similar sequences (approximate matches)

Correlation with other assays (exact sequence matches)

Relevant UniProtKB Entries

Percent Identity Matching Chains Protein Accession Entry Name
100.0 Repressor protein cI P03034 RPC1_LAMBD