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 PDB Entries

Structure ID Release Date Resolution Structure Title
1COP 1995-10-15 THREE-DIMENSIONAL DIMER STRUCTURE OF THE LAMBDA-CRO REPRESSOR IN SOLUTION AS DETERMINED BY HETERONUCLEAR MULTIDIMENSIONAL NMR
2A63 2006-06-06 Solution structure of a stably monomeric mutant of lambda Cro produced by substitutions in the ball-and-socket interface
2ORC 1998-05-27 CRO REPRESSOR INSERTION MUTANT K56-[DGEVK], NMR, 32 STRUCTURES
2OVG 2008-01-08 1.35 Lambda Cro Q27P/A29S/K32Q triple mutant at 1.35 A in space group P3221
2ECS 2008-01-08 1.4 Lambda Cro mutant Q27P/A29S/K32Q at 1.4 A in space group C2
1ORC 1996-12-23 1.54 CRO REPRESSOR INSERTION MUTANT K56-[DGEVK]
1D1M 1999-09-24 2.05 CRYSTAL STRUCTURE OF CRO K56-[DGEVK]-F58W MUTANT
1D1L 1999-10-06 2.1 CRYSTAL STRUCTURE OF CRO-F58W MUTANT
5CRO 1998-06-17 2.3 REFINED STRUCTURE OF CRO REPRESSOR PROTEIN FROM BACTERIOPHAGE LAMBDA
6CRO 1998-09-18 3.0 CRYSTAL STRUCTURE OF LAMBDA-CRO BOUND TO A CONSENSUS OPERATOR AT 3.0 ANGSTROM RESOLUTION
3ORC 1998-12-02 3.0 CRYSTAL STRUCTURE OF AN ENGINEERED CRO MONOMER BOUND NONSPECIFICALLY TO DNA
4CRO 1992-01-15 3.9 PROTEIN-DNA CONFORMATIONAL CHANGES IN THE CRYSTAL STRUCTURE OF A LAMBDA CRO-OPERATOR COMPLEX

Relevant UniProtKB Entries

Percent Identity Matching Chains Protein Accession Entry Name
100.0 Regulatory protein cro P03040 RCRO_LAMBD