Role of Prolyl Isomerization in Metamorphosis of the Clock Protein, KaiB

Abstract

Metamorphic proteins are an emerging class of proteins that defy the classic 'one structure-one fold' paradigm by alternating between two conformations despite having the same primary structure (i.e. sequence). KaiB is the only metamorphic protein known to exist in any circadian clock. It is a component of the cyanobacterial clock, adopting one fold during the day and a distinctly different one at night. Our recent findings suggest that three out of seven prolyl residues in KaiB- P63, P70 and P72- adopt the trans configuration during the day and cis at night. Also, there is a fourth prolyl residue, P51, which even though is trans in both folds is critical to clock mechanism. Binding assays of prolyl-to-alanyl KaiB mutants suggest hierarchical roles of the prolyl residues and raise the possibility that they isomerize sequentially: P63->P70 ->P72.