Abstract

Proteins are traditionally described by a deterministic relationship between the sequence, structure and function. The recognition of protein dynamics is increasing, the ambiguities in conformations and interaction patterns however, are still largely ignored. The structural multiplicity or dynamic disorder in protein complexes that contributes to regulated formation or function of the assemblies is referred to as fuzziness. Accumulating experimental evidence corroborates the importance of fuzziness in a variety of protein organizations and a wide spectrum of activities ranging from enzymatic catalysis to regulatory machines. Fuzzy regions could serve as transient interaction elements to mediate direct contacts or influence adjacent binding interfaces, as well as play a role as largely unstructured linkers and tails that may connect separate binding modules to increase their local concentration. Conformational diversity within protein complexes and higher-order assemblies results in a variety of regulatory pathways, including promoting/relieving intramolecular autoinhibition, facilitating allostery, or responding to posttranslational modifications via well-characterized mechanisms (see FuzDB: http://protdyn-database.org). I will provide an overview of how fuzziness interferes with existing and newly evolving protein functions.