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Both helical propensity and side‐chain hydrophobicity at a partially exposed site in α‐helix contribute to the thermodynamic stability of ubiquitin
Author(s) -
Loladze Vakhtang V.,
Makhatadze George I.
Publication year - 2004
Publication title -
proteins: structure, function, and bioinformatics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.699
H-Index - 191
eISSN - 1097-0134
pISSN - 0887-3585
DOI - 10.1002/prot.20283
Subject(s) - thermostability , helix (gastropod) , chemistry , ubiquitin , differential scanning calorimetry , residue (chemistry) , side chain , chemical stability , amino acid residue , crystallography , biophysics , biochemistry , peptide sequence , biology , thermodynamics , organic chemistry , polymer , enzyme , ecology , physics , snail , gene
Improving helical propensity of residues was proposed as one of the approaches to increase protein stability. Here the contribution of the helix propensity and hydrophobicity of residues at partially buried positions of α‐helix to the stability of a model protein—ubiquitin— is explored. Thermodynamic stabilities of 13 ubiquitin variants with substitutions at a partially buried helical residue were measured by differential scanning calorimetry. It was found that the dynamic range of stabilities for different amino acid residues at this partially buried position is 3 times larger than that expected based on helical propensity alone. Correlation analysis shows that both helical propensity and hydrophobicity are important in defining the relative stabilities of the studied ubiquitin variants. These results provide experimental evidence that partially buried positions are potentially useful sites for engineering proteins with enhanced thermostability. Proteins 2005. © 2004 Wiley‐Liss, Inc.