Intrinsically Disordered Proteins: Chronology of a Discovery

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Intrinsically Disordered Proteins, Protein Structure, Protein Function, Protein Folding, Protein Misfolding, Structure-function Paradigm

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Intrinsic disorder is a new reality that appears to penetrate every corner of modern protein science. It is difficult to imagine that only 20 years ago the situation was completely different, and almost nobody had heard about ‘structure-less’ but functional proteins. As a matter of fact, for many at that time, this idea was completely heretical when viewed in light of the then dominating lock-and-key model describing the protein structure-function relationship, where a unique amino acid sequence defines a unique crystal-like 3D structure that serves as a prerequisite for a unique function of a protein. It seems like the entire field of protein intrinsic disorder has magically emerged at the turn of the century due to a revelation to a small group of researchers. Although this may very well be true, literature shows that the first observations contradicting the lock-and-key view of protein functionality started to appear almost immediately after this model was proposed. The goal of this article is to provide a brief chronology (though admittedly a subjective one) of the events in the field of protein science that eventually culminated in the discovery of the protein intrinsic disorder phenomenon. The entire process represents a good example of the “dwarf standing on the shoulders of giants” (Latin: nanos gigantum humeris insidentes) metaphor, where the truth is discovered by building on previous discoveries.

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Biophysical Chemistry, v. 279, art. 106694