| Abstract: | ["Specific molecular recognition has long been equated with a well-defined set of contacts, which devoid of conformational and interaction ambiguities. Higher-order assemblies, which have emerged across a wide spectrum of the biological landscape in recent years, including amyloids and prions, various kinds of signalosomes, nuclear and cytoplasmic granules however cannot be characterized using the classical structure-function principles owing to their variable stoichiometry and heterogeneous conformations. Are there common biophysical principles at play for the different types of higher-order structures?\r\nA common feature of higher-order assemblies is the involvement of low-complexity domains (LCDs) and intrinsically disordered regions (IDRs), which propel phase transition and may alternatively either fold into ensembles of structured conformations or remain largely disordered, even exhibiting a fast exchange of conformations in their bound states, referred as fuzzy structures. Conformational diversity of any kind, either static or dynamic, has an impact on the regulated formation and function of higher-order assemblies. Fuzzy regions serve either as direct interaction elements, or as largely unstructured linkers and tails within higher-order structures may connect separate binding modules to increase their local concentration, exert transient interactions to influence adjacent binding elements, facilitate allostery, or promote intramolecular autoinhibition via well-characterized mechanisms (see also in FuzDB, http:\/\/protdyn-database.org)."] |
