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Access through your institution Buy or subscribe Interpreting function in terms of specific three-dimensional structure has dominated thinking about proteins for more than 100 years,

starting with the lock-and-key proposal of Fischer1 and continuing with the equating of denaturation with loss of specific structure by Wu2 and independently at a slightly later date by

Mirsky and Pauling3. This dependence of function on structure is even embedded in our language: unfolded protein and denatured protein are used interchangeably. Furthermore, the avalanche of

protein three-dimensional structures determined by X-ray diffraction and by nuclear magnetic resonance (NMR)4 has diverted attention away from alternative views. Numerous counterexample

proteins have surfaced over the years—proteins for which lack of three-dimensional structure is required for function. One clear example is calcineurin, a serine/threonine phosphatase that

becomes activated by the binding of the Ca2+–calmodulin complex to a region that exists as a disordered ensemble5,6. The disorder spans the calmodulin binding site and is essential for

calcineurin function. That is, when calmodulin binds to its target helix, the helix becomes completely surrounded7. Thus, the open, flexible disordered region of calcineurin provides the

space needed by calmodulin so it can completely surround its target helix. This is a preview of subscription content, access via your institution ACCESS OPTIONS Access through your

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AUTHORS AND AFFILIATIONS * professor of biophysics at the School of Molecular Biosciences, Washington State University, Pullman, 99124, WA A. Keith Dunker * professor and director at the

Center for Information, Science and Technology, Temple University, Philadelphia, 19122, PA Zoran Obradovic Authors * A. Keith Dunker View author publications You can also search for this

author inPubMed Google Scholar * Zoran Obradovic View author publications You can also search for this author inPubMed Google Scholar RIGHTS AND PERMISSIONS Reprints and permissions ABOUT

THIS ARTICLE CITE THIS ARTICLE Dunker, A., Obradovic, Z. The protein trinity—linking function and disorder. _Nat Biotechnol_ 19, 805–806 (2001). https://doi.org/10.1038/nbt0901-805 Download

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