COSMIC analysis of the major alpha-helix of barnase during folding.


The structures of transition states and intermediates in protein folding may be analysed by protein engineering methods that remove simple interactions that stabilize the folded state. We have now extended the range and reliability of the procedure by using the COSMIC (Combination of Sequential Mutant Interaction Cycles) technique, in which a series of double-mutant cycles is constructed. In each cycle, the side-chains of two amino acid residues that interact in the folded state are mutated separately and together. Kinetic and equilibrium measurements on folding for each cycle show unambiguously whether or not two residues interact during protein folding. A series of such cycles has been constructed to leapfrog along the major alpha-helix of barnase, comprising residues 6 to 18. The helix is found to be intact from its C terminus to residue 12 but begins to unwind towards the N terminus in both the transition state for unfolding and in a folding intermediate. Study holds ProTherm entries: 7459, 7460, 7461, 7462 Extra Details: protein folding; folding pathway;,folding intermediate

Submission Details


Submitter: Connie Wang

Submission Date: April 24, 2018, 8:34 p.m.

Version: 1

Publication Details
Horovitz A;Serrano L;Fersht AR,J. Mol. Biol. (1991) COSMIC analysis of the major alpha-helix of barnase during folding. PMID:2023260
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 Ribonuclease P00648 RNBR_BACAM
97.3 Ribonuclease P35078 RN_BACCI