Structural differences between thermophilic and mesophilic membrane proteins

Authors

  • Alejandro D. Meruelo,

    1. Medical Scientist Training Program, UCLA-DOE Institute for Genomics and Proteomics, Molecular Biology Institute, UCLA, Los Angeles, California 90095-1570
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  • Seong Kyu Han,

    1. Division of Molecular and Life Science, Pohang University of Science and Technology, Pohang, Korea
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  • Sanguk Kim,

    1. Division of Molecular and Life Science, Pohang University of Science and Technology, Pohang, Korea
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  • James U. Bowie

    Corresponding author
    1. Department of Chemistry and Biochemistry, UCLA-DOE Institute for Genomics and Proteomics, Molecular Biology Institute, UCLA, Los Angeles, California 90095-1570
    • Department of Chemistry and Biochemistry, UCLA-DOE Institute for Genomics and Proteomics, Molecular Biology Institute, UCLA, Los Angeles, California 90095-1570
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Abstract

The evolutionary adaptations of thermophilic water-soluble proteins required for maintaining stability at high temperature have been extensively investigated. Little is known about the adaptations in membrane proteins, however. Here, we compare many properties of mesophilic and thermophilic membrane protein structures, including side-chain burial, packing, hydrogen bonding, transmembrane kinks, loop lengths, hydrophobicity, and other sequence features. Most of these properties are quite similar between mesophiles and thermophiles although we observe a slight increase in side-chain burial and possibly a slight decrease in the frequency of transmembrane kinks in thermophilic membrane protein structures. The most striking difference is the increased hydrophobicity of thermophilic transmembrane helices, possibly reflecting more stringent hydrophobicity requirements for membrane partitioning at high temperature. In agreement with prior work examining transmembrane sequences, we find that thermophiles have an increase in small residues (Gly, Ala, Ser, and Val) and a strong suppression of Cys. We also find a relative dearth of most strongly polar residues (Asp, Asn, Glu, Gln, and Arg). These results suggest that in thermophiles, there is significant evolutionary pressure to offload destabilizing polar amino acids, to decrease the entropy cost of side chain burial, and to eliminate thermally sensitive amino acids.

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