A water mediated electrostatic interaction gives thermal stability to the "tail" region of the GrpE protein from E. coli

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Abstract

The GrpE protein from E. coli is a homodimer with an unusual structure of two long paired α-helices from each monomer interacting in a parallel arrangement to form a "tail" at the N-terminal end. Using site-directed mutagenesis, we show that there is a key electrostatic interaction involving R57 (mediated by a water molecule) that provides thermal stability to this "tail" region. The R57A mutant showed a drop in T m of 8.5°C and a smaller ΔH u (unfolding) compared to wild-type for the first unfolding transition, but no significant decrease in dimer stability as shown through equilibrium analytical ultracentrifugation studies. Another mutant (E94A) at the dimer interface showed a decrease in ΔH u but no drop in T m for the second unfolding transition and a slight increase in dimer stability.

Original languageEnglish
Pages (from-to)239-245
Number of pages7
JournalProtein Journal
Volume26
Issue number4
DOIs
StatePublished - Jun 2007

Funding

This work was supported in part by NIH Grant GM64406 to A. F. M.; additionally we would like to thank Josh Hays at the Keck Biophysical Facility at Northwestern University for performing the sedimentation experiments and Debbie Ang for the DA262 strain of E. coli. The development of the UltraScan software is supported by the National Science Foundation through grant DBI-9974819 to B. Demeler, and by the San Antonio Life Science Institute through grant1000–1642.

Funder number
grant1000–1642
DBI-9974819
R15GM064406

    Keywords

    • Electrostatic interactions
    • GrpE
    • Oligomerization
    • Protein stability
    • Salt bridge

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