Interactions involving disordered protein regions are landmarks of regulatory processes in both eukaryotes and viruses,and contribute as well as to host recognition by prokaryotes. These interactions often result in structurally heterogeneous, fuzzy complexes, which exhibit different binding modes with different partners or cellular condition, to generate complex responses in several biochemical pathways. Fuzziness results from the interplay of multiple interaction motifs that enable signaling specificity with a variety of interaction partners modulated by post-translational modifications, alternative splicing or ligand binding. Weak, redundant contacts are also present in biomolecular condensates and serve as driving forces of liquid-liquid phase separation. Fuzzy interactions may also occur intramolecularly, connecting the flexible regulatory capacity of disordered domains with the structure-based efficiency of enzymatic processes or the specificity motif recognition of globular domains.
Experimental evidence glimpsing into the molecular mechanisms of how weak, transient interactions impact interactions of proteins and their higher-order organization is rapidly increasing. Advances in structure determination techniques attain higher spatial and temporal resolution and provide an in-depth characterization of conformational ensembles in fuzzy protein complexes. Awareness of protein fuzziness enables establishing of functional links between heterogeneous conformational ensembles formed by protein assemblies, and their roles in a variety of biological processes. This knowledge can be exploited to decipher the molecular mechanisms behind complex signaling processes, as well as the regulated formation and function of membraneless organelles.
The goal of this Research Topic is to provide an overview of recent advances in the characterization of fuzzy interactions. Elucidating the molecular mechanisms and principles of fuzzy protein complexes will contribute to the endeavor of revising the classical structure-function paradigm to be applicable to cellular conditions.
In this Research Topic we welcome original contributions, perspectives and reviews shining light into the broad subject of fuzzy interactions in proteins including, but not restricted to:
• Identification and experimental characterization of fuzzy complexes
• Physical models explaining the properties of fuzzy complexes
• Functional significance of fuzzy complexes in signaling and aggregation
• Connection with other disordered states, such as glasses or liquid-phase separated states
• Integration of disordered and globular domains in multidomain proteins and complexes.
A list of accepted article types including descriptions can be found at this
linkInteractions involving disordered protein regions are landmarks of regulatory processes in both eukaryotes and viruses,and contribute as well as to host recognition by prokaryotes. These interactions often result in structurally heterogeneous, fuzzy complexes, which exhibit different binding modes with different partners or cellular condition, to generate complex responses in several biochemical pathways. Fuzziness results from the interplay of multiple interaction motifs that enable signaling specificity with a variety of interaction partners modulated by post-translational modifications, alternative splicing or ligand binding. Weak, redundant contacts are also present in biomolecular condensates and serve as driving forces of liquid-liquid phase separation. Fuzzy interactions may also occur intramolecularly, connecting the flexible regulatory capacity of disordered domains with the structure-based efficiency of enzymatic processes or the specificity motif recognition of globular domains.
Experimental evidence glimpsing into the molecular mechanisms of how weak, transient interactions impact interactions of proteins and their higher-order organization is rapidly increasing. Advances in structure determination techniques attain higher spatial and temporal resolution and provide an in-depth characterization of conformational ensembles in fuzzy protein complexes. Awareness of protein fuzziness enables establishing of functional links between heterogeneous conformational ensembles formed by protein assemblies, and their roles in a variety of biological processes. This knowledge can be exploited to decipher the molecular mechanisms behind complex signaling processes, as well as the regulated formation and function of membraneless organelles.
The goal of this Research Topic is to provide an overview of recent advances in the characterization of fuzzy interactions. Elucidating the molecular mechanisms and principles of fuzzy protein complexes will contribute to the endeavor of revising the classical structure-function paradigm to be applicable to cellular conditions.
In this Research Topic we welcome original contributions, perspectives and reviews shining light into the broad subject of fuzzy interactions in proteins including, but not restricted to:
• Identification and experimental characterization of fuzzy complexes
• Physical models explaining the properties of fuzzy complexes
• Functional significance of fuzzy complexes in signaling and aggregation
• Connection with other disordered states, such as glasses or liquid-phase separated states
• Integration of disordered and globular domains in multidomain proteins and complexes.
A list of accepted article types including descriptions can be found at this
link