The molecular basis of cooperativity in protein folding. Thermodynamic dissection of interdomain interactions in phosphoglycerate kinase.


In the presence of guanidine hydrochloride, phosphoglycerate kinase from yeast can be reversibly denatured by either heating or cooling the protein solution above or below room temperature [Griko, Y. V., Venyaminov, S. Y., & Privalov, P. L. (1989) FEBS Lett. 244, 276-278]. The heat denaturation of PGK is characterized by the presence of a single peak in the excess heat capacity function obtained by differential scanning calorimetry. The transition curve approaches the two-state mechanism, indicating that the two domains of the molecule display strong cooperative interactions and that partially folded intermediates are not largely populated during the transition. On the contrary, the cold denaturation is characterized by the presence of two peaks in the heat capacity function. Analysis of the data indicates that at low temperatures the two domains behave independently of each other. The crystallographic structure of PGK has been used to identify the nature of the interactions between the two domains. These interactions involve primarily the apposition of two hydrophobic surfaces of approximately 480 A2 and nine hydrogen bonds. This information, in conjunction with experimental thermodynamic values for hydrophobic, hydrogen bonding interactions and statistical thermodynamic analysis, has been used to quantitatively account for the folding/unfolding behavior of PGK. It is shown that this type of analysis accurately predicts the cooperative behavior of the folding/unfolding transition and its dependence on GuHCl concentration. Study holds ProTherm entries: 3972 Extra Details: interprotein stability; domain interactions; cooperative interactions;,hydrophobic surfaces; hydrogen bonds

Submission Details


Submitter: Connie Wang

Submission Date: April 24, 2018, 8:23 p.m.

Version: 1

Publication Details
Freire E;Murphy KP;Sanchez-Ruiz JM;Galisteo ML;Privalov PL,Biochemistry (1992) The molecular basis of cooperativity in protein folding. Thermodynamic dissection of interdomain interactions in phosphoglycerate kinase. PMID:1731874
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
1QPG 1996-01-04T00:00:00+0000 2.4 3-PHOSPHOGLYCERATE KINASE, MUTATION R65Q
3PGK 1982-07-15T00:00:00+0000 2.5 The structure of yeast phosphoglycerate kinase at 0.25 nm resolution

Relevant UniProtKB Entries

Percent Identity Matching Chains Protein Accession Entry Name
94.5 Phosphoglycerate kinase Q6FKY1 PGK_CANGA
100.0 Phosphoglycerate kinase P00560 PGK_YEAST