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
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