Evidence for a three-state model of protein folding from kinetic analysis of ubiquitin variants with altered core residues.


Abstract

To elucidate the kinetic importance of structural intermediates in single-domain proteins, we measured the effect of solution conditions and amino-acid changes at a central core residue of ubiquitin (Val 26) on the kinetics of folding and unfolding. Kinetic analysis in terms of a sequential three-state mechanism provides insight into the contribution of specific interactions within the ubiquitin core to the structural stability of the native and intermediate states. The observations that disruptive mutations and/or addition of denaturants result in an apparent two-state folding process with slower rates is explained by the destabilization of a partially folded intermediate, which is in rapid equilibrium with unfolded states. The model predicts that under sufficiently stabilizing conditions kinetic intermediates may become populated even for proteins showing apparent two-state kinetics. Study holds ProTherm entries: 3090, 3091, 3092, 3093, 3094 Extra Details: ubiquitin; protein folding; kinetic analysis; core residue;,structural stability; intermediate state; specific interactions

Submission Details

ID: evu4C52R4

Submitter: Connie Wang

Submission Date: April 24, 2018, 8:21 p.m.

Version: 1

Publication Details
Khorasanizadeh S;Peters ID;Roder H,Nat. Struct. Biol. (1996) Evidence for a three-state model of protein folding from kinetic analysis of ubiquitin variants with altered core residues. PMID:8564547
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