Biochim Biophys Acta Proteins Proteom 2019 Feb 28. Epub 2019 Feb 28.
Institute of Enzymology, Research Centre for Natural Sciences of the Hungarian Academy of Sciences, Budapest, Hungary; VIB Center for Structural Biology (CSB), Brussels, Belgium; Structural Biology Brussels (SBB), Vrije Universiteit Brussel (VUB), Brussels, Belgium. Electronic address:
Proteins are the basic functional units of the cell, carrying out myriads of functions essential for life. There are countless reports in molecular cell biology addressing the functioning of proteins under physiological and pathological conditions, aiming to understand life at the atomistic-molecular level and thereby being able to develop remedies against diseases. The central theme in most of these studies is that the functional unit under study is the protein itself. Recent rapid progress has radically challenged and extended this protein-function paradigm, by demonstrating that novel function(s) may emerge when proteins form dynamic and non-stoichiometric supramolecular assemblies. There is an increasing number of cases for such collective functions, such as targeting, localization, protection/shielding and filtering effects, as exemplified by signaling complexes and prions, biominerals and mucus, amphibian adhesions and bacterial biofilms, and a broad range of membraneless organelles (bio-condensates) formed by liquid-liquid phase separation in the cell. In this short review, we show that such non-stoichiometric organization may derive from the heterogeneity of the system, a mismatch in valency and/or geometry of the partners, and/or intrinsic structural disorder and multivalency of the component proteins. Either way, the resulting functional features cannot be simply described by, or predicted from, the properties of the isolated single protein(s), as they belong to the collection of proteins.
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