A deeper understanding of how living systems use protein shape shifting to control cellular processes would allow better design of therapeutics that can alter these shapes in order to turn proteins on and off and control disease, Deniz notes.
Head or Tail?
In the new study, the researchers examined a protein known as Rop (repressor of primer), expressed in E. coli bacteria, which binds to RNA to regulate the number of copies of plasmid genes produced within the bacteria. This small "homodimer" is made up of two identical hairpin coils of amino acids, and has often been used as a model system to study protein structure and stability.
The protein has been found in two different conformations: the "anti" wild type (natural) conformation occurs when the "head" of one hairpin is paired with the "tail" of the second, and the "syn" structure is made up of the two bound head-to-head. The anti structure is thought to be the active conformation that binds to RNA, while the syn structurefound in a mutantis inactive.
But theorist Onuchic and his coworkers had proposed that there is a delicate balance of energy for the syn and anti structures, with mutations or conditions being able to alter this balance. They predicted that certain mutations in the protein sequence would allow a single sequence to populate both structures, which they felt might explain puzzling
|Contact: Keith McKeown|
Scripps Research Institute