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Structural and energetic consequences of mutations in a solvated hydrophobic cavity.

Adamek DH, Guerrero L, Blaber M, Caspar DL
J Mol Biol 346 307-18 (2005)
Related entries: 1s0l, 1t4q, 1too, 1twe, 1twm

Cited: 19 times
EuropePMC logo PMID: 15663946

Abstract

The structural and energetic consequences of modifications to the hydrophobic cavity of interleukin 1-beta (IL-1beta) are described. Previous reports demonstrated that the entirely hydrophobic cavity of IL-1beta contains positionally disordered water. To gain a better understanding of the nature of this cavity and the water therein, a number of mutant proteins were constructed by site-directed mutagenesis, designed to result in altered hydrophobicity of the cavity. These mutations involve the replacement of specific phenylalanine residues, which circumscribe the cavity, with tyrosine, tryptophan, leucine and isoleucine. Using differential scanning calorimetry to determine the relative stabilities of the wild-type and mutant proteins, we found all of the mutants to be destabilizing. X-ray crystallography was used to identify the structural consequences of the mutations. No clear correlation between the hydrophobicities of the specific side-chains introduced and the resulting stabilities was found.

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  2. Determination of solvent content in cavities in IL-1beta using experimentally phased electron density. Quillin ML, Wingfield PT, Matthews BW. Proc Natl Acad Sci U S A 103 19749-19753 (2006)
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  10. Structural and functional comparison of cytokine interleukin-1 beta from chicken and human. Cheng CS, Chen WT, Lee LH, Chen YW, Chang SY, Lyu PC, Yin HS. Mol Immunol 48 947-955 (2011)
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