Effects of mutations on the thermodynamics of a protein folding reaction: implications for the mechanism of formation of the intermediate and transition states.


Abstract

We have measured changes in heat capacity, entropy, and enthalpy for each step in the folding reaction of CD2.d1 and evaluated the effects of core mutations on these properties. All wild-type and mutant forms fold through a rapidly formed intermediate state that precedes the rate-limiting transition state. Mutations have a pronounced effect on the enthalpy of both the intermediate and folded states, but in all cases a compensatory change in entropy results in a small net free-energy change. While the enthalpy change in the folded state can be attributed to a loss of van der Waals interactions, it has already been shown that changes in the stability of the intermediate are dominated by changes in secondary structure propensity [Lorch et al. (1999) Biochemistry 38, 1377-1385]. It follows that the thermodynamic basis of beta-propensity is enthalpic in origin. The effects of mutations on the enthalpy and entropy of the transition state are smaller than on the ground states. This relative insensitivity to mutation is discussed in the light of theories concerning the nature of the rate-limiting barrier in folding reactions. Study holds ProTherm entries: 7943, 7944, 7945, 7946, 7947, 7948, 7949, 7950, 7951, 7952 Extra Details: U-I core mutations; intermediate state; van der Waals interactions;,secondary structure propensity; rate-limiting barrier

Submission Details

ID: Epf5MjRU

Submitter: Connie Wang

Submission Date: April 24, 2018, 8:35 p.m.

Version: 1

Publication Details
Lorch M;Mason JM;Sessions RB;Clarke AR,Biochemistry (2000) Effects of mutations on the thermodynamics of a protein folding reaction: implications for the mechanism of formation of the intermediate and transition states. PMID:10727243
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
1T6W 2005-02-15 RATIONAL DESIGN OF A CALCIUM-BINDING ADHESION PROTEIN NMR, 20 STRUCTURES
1CCZ 1999-04-05 1.8 CRYSTAL STRUCTURE OF THE CD2-BINDING DOMAIN OF CD58 (LYMPHOCYTE FUNCTION-ASSOCIATED ANTIGEN 3) AT 1.8-A RESOLUTION
1CDC 1995-09-15 2.0 CD2, N-TERMINAL DOMAIN (1-99), TRUNCATED FORM
1A64 1998-05-27 2.0 ENGINEERING A MISFOLDED FORM OF RAT CD2
1A6P 1998-06-17 2.08 ENGINEERING OF A MISFOLDED FORM OF CD2
2DRU 2006-07-04 2.6 Crystal structure and binding properties of the CD2 and CD244 (2B4) binding protein, CD48
1HNG 1995-02-07 2.8 CRYSTAL STRUCTURE AT 2.8 ANGSTROMS RESOLUTION OF A SOLUBLE FORM OF THE CELL ADHESION MOLECULE CD2
1A7B 1998-06-17 3.1 ENGINEERING A MISFOLDED FORM OF CD2

Relevant UniProtKB Entries

Percent Identity Matching Chains Protein Accession Entry Name
99.7 T-cell surface antigen CD2 P08921 CD2_RAT