Emergent functions of proteins in non-stoichiometric supramolecular assemblies

• Published in: Biochimica et biophysica acta. Proteins and proteomics 2019-10, Vol.1867 (10), p.970-979
• Main Authors: Pancsa, Rita, Schad, Eva, Tantos, Agnes, Tompa, Peter
• Format: Article
• Language: English
• Subjects: Animals; Bacteria - chemistry; Bacteria - metabolism; Bacterial Proteins - chemistry; Bacterial Proteins - metabolism; Biomolecular condensate; Contextual function; Dynamic assembly; Emergent function; Humans; Intrinsically disordered protein; Intrinsically Disordered Proteins - chemistry; Intrinsically Disordered Proteins - metabolism; Membraneless organelle; Multiprotein Complexes - chemistry; Multiprotein Complexes - metabolism; Phase separation
• ISSN: 1570-9639; 1878-1454
• DOI: 10.1016/j.bbapap.2019.02.007

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. •Proteins, the basic functional units of the cell often form loosely-associated assemblies in the cell.•In these assemblies the molar ratio of proteins is not well defined, i.e. they lack exact “stoichiometry”.•The function of these assemblies cannot be predicted from that of individual proteins.•Their function pertains to the whole assembly, i.e. it is an emergent property.