Premium
A polymorphic position in electron transfer flavoprotein modulates kinetic stability as evidenced by thermal stress
Author(s) -
Henriques Bárbara J.,
Fisher Mark T.,
Bross Peter,
Gomes Cláudio M.
Publication year - 2011
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2011.01.002
Subject(s) - flavoprotein , groel , chemistry , flavin adenine dinucleotide , kinetics , biophysics , electron transfer , cofactor , flavin group , biochemistry , photochemistry , enzyme , biology , physics , escherichia coli , quantum mechanics , gene
The electron transfer flavoprotein (ETF) is a hub interacting with at least 11 mitochondrial flavoenzymes and linking them to the respiratory chain. Here we report the effect of the ETFα‐T/I171 polymorphism on protein conformation and kinetic stability under thermal stress. Although variants have comparable thermodynamic stabilities, kinetically their behavior is rather distinct as ETFα‐T171 displays increased susceptibility to cofactor flavin adenine dinucleotide (FAD) loss and enhanced kinetics of inactivation during thermal stress. Mimicking a fever episode yields substantial activity loss. However, the presence of substoichiometric concentrations of GroEL is sufficient to act as an effective buffer against long‐term thermal denaturation. Our investigations are compatible with the notion that the ETFα‐T171 variant displays an altered conformational landscape that results in reduced protein function under thermal stress.