Surface salt bridges stabilize the GCN4 leucine zipper.


We present a study of the role of salt bridges in stabilizing a simplified tertiary structural motif, the coiled-coil. Changes in GCN4 sequence have been engineered that introduce trial patterns of single and multiple salt bridges at solvent exposed sites. At the same sites, a set of alanine mutants was generated to provide a reference for thermodynamic analysis of the salt bridges. Introduction of three alanines stabilizes the dimer by 1.1 kcal/mol relative to the wild-type. An arrangement corresponding to a complex type of salt bridge involving three groups stabilizes the dimer by 1.7 kcal/ mol, an apparent elevation of the melting temperature relative to wild type of about 22 degrees C. While identifying local from nonlocal contributions to protein stability is difficult, stabilizing interactions can be identified by use of cycles. Introduction of alanines for side chains of lower helix propensity and complex salt bridges both stabilize the coiled-coil, so that combining the two should yield melting temperatures substantially higher than the starting species, approaching those of thermophilic sequences. Study holds ProTherm entries: 3425, 3426, 3427, 3428, 3429, 3430, 3431, 3432, 3433, 3434, 14215, 14216, 14217, 14218, 14219, 14220, 14221, 14222, 14223 Extra Details: GCN4; leucine zipper; salt bridge; thermal stability

Submission Details

ID: gRfVTChx

Submitter: Connie Wang

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

Version: 1

Publication Details
Spek EJ;Bui AH;Lu M;Kallenbach NR,Protein Sci. (1998) Surface salt bridges stabilize the GCN4 leucine zipper. PMID:9828010
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 General control protein GCN4 P03069 GCN4_YEAST