The structure of the major transition state for folding of an FF domain from experiment and simulation.


Abstract

We have analysed the transition state of folding of the four-helix FF domain from HYPA/FBP11 by high-resolution experiment and simulation as part of a continuing effort to understand the principles of folding and the refinement of predictive methods. The major transition state for folding was subjected to a Phi-value analysis utilising 50 mutants. The transition state contained a nucleus for folding centred around the end of helix 1 (H1) and the beginning of helix 2 (H2). Secondary structure in this region was fully formed (PhiF=0.9-1) and tertiary interactions were well developed. Interactions in the distal part of the native structure were weak (PhiF=0-0.2). The hydrophobic core and other parts of the protein displayed intermediate Phi-values, suggesting that interactions coalesce as the end of H1 and beginning of H2 are in the process of being formed. The distribution of Phi-values resembled that of barnase, which folds via an intermediate, rather than that of CI2 which folds by a concerted nucleation-condensation mechanism. The overall picture of the transition state structure identified in molecular dynamics simulations is in qualitative agreement, with the turn connecting H1 and H2 being formed, a loosened core, and H4 partially unfolded and detached from the core. There are some differences in the details and interpretation of specific Phi-values. Study holds ProTherm entries: 19104, 19105, 19106, 19107, 19108, 19109, 19110, 19111, 19112, 19113, 19114, 19115, 19116, 19117, 19118, 19119, 19120, 19121, 19122, 19123, 19124, 19125, 19126, 19127, 19128, 19129, 19130, 19131, 19132, 19133, 19134, 19135, 19136, 19137, 19138, 19139, 19140, 19141, 19142, 19143, 19144, 19145, 19146, 19147, 19148, 19149, 19150, 19151 Extra Details: FF domain protein folding; phi-value analysis; FF domain; protein engineering; molecular dynamics simulation

Submission Details

ID: vLrxQtqX

Submitter: Connie Wang

Submission Date: April 24, 2018, 8:51 p.m.

Version: 1

Publication Details
Jemth P;Day R;Gianni S;Khan F;Allen M;Daggett V;Fersht AR,J. Mol. Biol. (2005) The structure of the major transition state for folding of an FF domain from experiment and simulation. PMID:15935381
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 PDB Entries

Structure ID Release Date Resolution Structure Title
2L5F 2011-05-11 Solution structure of the tandem WW domains from HYPA/FBP11
2LKS 2012-01-11 Ff11-60
1YWJ 2005-04-12 Structure of the FBP11WW1 domain
2KZG 2010-09-29 A Transient and Low Populated Protein Folding Intermediate at Atomic Resolution
1ZR7 2006-05-30 Solution structure of the first WW domain of FBP11
1UZC 2004-04-05 THE STRUCTURE OF AN FF DOMAIN FROM HUMAN HYPA/FBP11
1YWI 2005-04-12 Structure of the FBP11WW1 domain complexed to the peptide APPTPPPLPP
2CQN 2005-11-20 Solution structure of the FF domain of human Formin-binding protein 3
2DYF 2006-10-24 Solution structure of the first WW domain of FBP11 / HYPA (FBP11 WW1) complexed with a PL (PPLP) motif peptide ligand
2L9V 2011-09-28 NMR structure of the FF domain L24A mutant's folding transition state

Relevant UniProtKB Entries

Percent Identity Matching Chains Protein Accession Entry Name
100.0 Pre-mRNA-processing factor 40 homolog A Q9R1C7 PR40A_MOUSE
100.0 Pre-mRNA-processing factor 40 homolog A O75400 PR40A_HUMAN