Reverse hydrophobic effects relieved by amino-acid substitutions at a protein surface.


Abstract

It is rare for amino-acid substitutions on the surface of proteins to have large stabilizing or destabilizing effects. Nevertheless, one substitution of this type, the Tyr 26----Cys mutation in lambda Cro, increases the melting temperature of the protein by 11 degrees C and the stability by 2.2 kcal mol-1. Here we show that the stability of Cro can be increased by many different amino-acid substitutions at position 26, with increasing stability showing a good correlation with decreasing side-chain hydrophobicity. As Tyr 26 is hyper-exposed to solvent in the Cro crystal structure, we suggest that wild-type and variant proteins with other hydrophobic side chains at position 26 are destabilized as a result of a reverse hydrophobic effect caused by the side chain being more exposed to solvent in the native than in the denatured state. Study holds ProTherm entries: 880, 881, 882, 883, 884, 885, 886, 887, 888, 13440, 13441, 13442, 13443, 13444, 13445, 13446, 13447 Extra Details: stability; lambda Cro; hydrophobic effect;,amino acid substitution; protein surface

Submission Details

ID: tK4R2ccu3

Submitter: Connie Wang

Submission Date: April 24, 2018, 8:16 p.m.

Version: 1

Publication Details
Pakula AA;Sauer RT,Nature (1990) Reverse hydrophobic effects relieved by amino-acid substitutions at a protein surface. PMID:2314475
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 Regulatory protein cro P03040 RCRO_LAMBD