%0 Journal Article %1 spongaOrderDisorderSarcomere2021 %A Sponga, Antonio %A Arolas, Joan L. %A Schwarz, Thomas C. %A Jeffries, Cy M. %A Rodriguez Chamorro, Ariadna %A Kostan, Julius %A Ghisleni, Andrea %A Drepper, Friedel %A Polyansky, Anton %A De Almeida Ribeiro, Euripedes %A Pedron, Miriam %A Zawadzka-Kazimierczuk, Anna %A Mlynek, Georg %A Peterbauer, Thomas %A Doto, Pierantonio %A Schreiner, Claudia %A Hollerl, Eneda %A Mateos, Borja %A Geist, Leonhard %A Faulkner, Georgine %A Kozminski, Wiktor %A Svergun, Dmitri I. %A Warscheid, Bettina %A Zagrovic, Bojan %A Gautel, Mathias %A Konrat, Robert %A Djinović-Carugo, Kristina %C United States %D 2021 %J Science advances %K to_read %N 22 %R 10.1126/sciadv.abg7653 %T Order from Disorder in the Sarcomere: FATZ Forms a Fuzzy but Tight Complex and Phase-Separated Condensates with $\alpha$-Actinin. %V 7 %X In sarcomeres, $\alpha$-actinin cross-links actin filaments and anchors them to the Z-disk. FATZ (filamin-, $\alpha$-actinin-, and telethonin-binding protein of the Z-disk) proteins interact with $\alpha$-actinin and other core Z-disk proteins, contributing to myofibril assembly and maintenance. Here, we report the first structure and its cellular validation of $\alpha$-actinin-2 in complex with a Z-disk partner, FATZ-1, which is best described as a conformational ensemble. We show that FATZ-1 forms a tight fuzzy complex with $\alpha$-actinin-2 and propose an interaction mechanism via main molecular recognition elements and secondary binding sites. The obtained integrative model reveals a polar architecture of the complex which, in combination with FATZ-1 multivalent scaffold function, might organize interaction partners and stabilize $\alpha$-actinin-2 preferential orientation in Z-disk. Last, we uncover FATZ-1 ability to phase-separate and form biomolecular condensates with $\alpha$-actinin-2, raising the question whether FATZ proteins can create an interaction hub for Z-disk proteins through membraneless compartmentalization during myofibrillogenesis.

@article{spongaOrderDisorderSarcomere2021, abstract = {In sarcomeres, {$\alpha$}-actinin cross-links actin filaments and anchors them to the Z-disk. FATZ (filamin-, {$\alpha$}-actinin-, and telethonin-binding protein of the Z-disk) proteins interact with {$\alpha$}-actinin and other core Z-disk proteins, contributing to myofibril assembly and maintenance. Here, we report the first structure and its cellular validation of {$\alpha$}-actinin-2 in complex with a Z-disk partner, FATZ-1, which is best described as a conformational ensemble. We show that FATZ-1 forms a tight fuzzy complex with {$\alpha$}-actinin-2 and propose an interaction mechanism via main molecular recognition elements and secondary binding sites. The obtained integrative model reveals a polar architecture of the complex which, in combination with FATZ-1 multivalent scaffold function, might organize interaction partners and stabilize {$\alpha$}-actinin-2 preferential orientation in Z-disk. Last, we uncover FATZ-1 ability to phase-separate and form biomolecular condensates with {$\alpha$}-actinin-2, raising the question whether FATZ proteins can create an interaction hub for Z-disk proteins through membraneless compartmentalization during myofibrillogenesis.}, added-at = {2024-05-17T13:01:35.000+0200}, address = {United States}, author = {Sponga, Antonio and Arolas, Joan L. and Schwarz, Thomas C. and Jeffries, Cy M. and Rodriguez Chamorro, Ariadna and Kostan, Julius and Ghisleni, Andrea and Drepper, Friedel and Polyansky, Anton and De Almeida Ribeiro, Euripedes and Pedron, Miriam and {Zawadzka-Kazimierczuk}, Anna and Mlynek, Georg and Peterbauer, Thomas and Doto, Pierantonio and Schreiner, Claudia and Hollerl, Eneda and Mateos, Borja and Geist, Leonhard and Faulkner, Georgine and Kozminski, Wiktor and Svergun, Dmitri I. and Warscheid, Bettina and Zagrovic, Bojan and Gautel, Mathias and Konrat, Robert and {Djinovi{\'c}-Carugo}, Kristina}, biburl = {https://www.bibsonomy.org/bibtex/23433fea33b3cde1fa432b5515822030d/warscheidlab}, copyright = {Copyright {\copyright} 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).}, doi = {10.1126/sciadv.abg7653}, interhash = {6b6e827d8722d4cebbc43ae0ff651065}, intrahash = {3433fea33b3cde1fa432b5515822030d}, issn = {2375-2548}, journal = {Science advances}, keywords = {to_read}, langid = {english}, month = may, number = 22, pmcid = {PMC8163081}, pmid = {34049882}, timestamp = {2024-05-17T13:01:35.000+0200}, title = {Order from Disorder in the Sarcomere: {{FATZ}} Forms a Fuzzy but Tight Complex and Phase-Separated Condensates with {$\alpha$}-Actinin.}, volume = 7, year = 2021 }