Proteins don’t typically behave tractably. The molecular interaction between two proteins is often a lot more complicated than one fully formed protein fitting into another, lock-and-key style. Especially when considering the lightning-fast connections being formed, broken, and re-formed when signaling proteins interact. Some critical signaling proteins exist in highly disordered, or unfolded, forms and only fold into their final conformations when they encounter and engage their molecular dance partners.
But until Scripps Research Institute structural biologist Peter Wright and colleagues described the intricate and fast-paced dance between one of these “intrinsically disordered proteins” and its target, researchers were left to guess about the kinetics and structural changes involved in these pairings. Wright and his coauthors characterized the complex and fluid interaction between a disordered protein segment, the phosphorylated kinase–inducible activation domain (pKID) of the cAMP response element binding (CREB) transcription factor, and its binding partner, the KIX domain of the ...
