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Order from disorder in the sarcomere: FATZ forms a fuzzy but tight complex and phase-separated condensates with α-actinin

In sarcomeres, α-actinin cross-links actin filaments and anchors them to the Z-disk. FATZ (filamin-, α-actinin-, and telethonin-binding protein of the Z-disk) proteins interact with α-actinin and other core Z-disk proteins, contributing to myofibril assembly and maintenance. Here, we report the firs...

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Autores principales: Sponga, Antonio, Arolas, Joan L., Schwarz, Thomas C., Jeffries, Cy M., Rodriguez Chamorro, Ariadna, Kostan, Julius, Ghisleni, Andrea, Drepper, Friedel, Polyansky, Anton, De Almeida Ribeiro, Euripedes, Pedron, Miriam, Zawadzka-Kazimierczuk, Anna, Mlynek, Georg, Peterbauer, Thomas, Doto, Pierantonio, Schreiner, Claudia, Hollerl, Eneda, Mateos, Borja, Geist, Leonhard, Faulkner, Georgine, Kozminski, Wiktor, Svergun, Dmitri I., Warscheid, Bettina, Zagrovic, Bojan, Gautel, Mathias, Konrat, Robert, Djinović-Carugo, Kristina
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Association for the Advancement of Science 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8163081/
https://www.ncbi.nlm.nih.gov/pubmed/34049882
http://dx.doi.org/10.1126/sciadv.abg7653
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author Sponga, Antonio
Arolas, Joan L.
Schwarz, Thomas C.
Jeffries, Cy M.
Rodriguez Chamorro, Ariadna
Kostan, Julius
Ghisleni, Andrea
Drepper, Friedel
Polyansky, Anton
De Almeida Ribeiro, Euripedes
Pedron, Miriam
Zawadzka-Kazimierczuk, Anna
Mlynek, Georg
Peterbauer, Thomas
Doto, Pierantonio
Schreiner, Claudia
Hollerl, Eneda
Mateos, Borja
Geist, Leonhard
Faulkner, Georgine
Kozminski, Wiktor
Svergun, Dmitri I.
Warscheid, Bettina
Zagrovic, Bojan
Gautel, Mathias
Konrat, Robert
Djinović-Carugo, Kristina
author_facet Sponga, Antonio
Arolas, Joan L.
Schwarz, Thomas C.
Jeffries, Cy M.
Rodriguez Chamorro, Ariadna
Kostan, Julius
Ghisleni, Andrea
Drepper, Friedel
Polyansky, Anton
De Almeida Ribeiro, Euripedes
Pedron, Miriam
Zawadzka-Kazimierczuk, Anna
Mlynek, Georg
Peterbauer, Thomas
Doto, Pierantonio
Schreiner, Claudia
Hollerl, Eneda
Mateos, Borja
Geist, Leonhard
Faulkner, Georgine
Kozminski, Wiktor
Svergun, Dmitri I.
Warscheid, Bettina
Zagrovic, Bojan
Gautel, Mathias
Konrat, Robert
Djinović-Carugo, Kristina
author_sort Sponga, Antonio
collection PubMed
description In sarcomeres, α-actinin cross-links actin filaments and anchors them to the Z-disk. FATZ (filamin-, α-actinin-, and telethonin-binding protein of the Z-disk) proteins interact with α-actinin and other core Z-disk proteins, contributing to myofibril assembly and maintenance. Here, we report the first structure and its cellular validation of α-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 α-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 α-actinin-2 preferential orientation in Z-disk. Last, we uncover FATZ-1 ability to phase-separate and form biomolecular condensates with α-actinin-2, raising the question whether FATZ proteins can create an interaction hub for Z-disk proteins through membraneless compartmentalization during myofibrillogenesis.
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spelling pubmed-81630812021-06-07 Order from disorder in the sarcomere: FATZ forms a fuzzy but tight complex and phase-separated condensates with α-actinin Sponga, Antonio Arolas, Joan L. Schwarz, Thomas C. Jeffries, Cy M. Rodriguez Chamorro, Ariadna Kostan, Julius Ghisleni, Andrea Drepper, Friedel Polyansky, Anton De Almeida Ribeiro, Euripedes Pedron, Miriam Zawadzka-Kazimierczuk, Anna Mlynek, Georg Peterbauer, Thomas Doto, Pierantonio Schreiner, Claudia Hollerl, Eneda Mateos, Borja Geist, Leonhard Faulkner, Georgine Kozminski, Wiktor Svergun, Dmitri I. Warscheid, Bettina Zagrovic, Bojan Gautel, Mathias Konrat, Robert Djinović-Carugo, Kristina Sci Adv Research Articles In sarcomeres, α-actinin cross-links actin filaments and anchors them to the Z-disk. FATZ (filamin-, α-actinin-, and telethonin-binding protein of the Z-disk) proteins interact with α-actinin and other core Z-disk proteins, contributing to myofibril assembly and maintenance. Here, we report the first structure and its cellular validation of α-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 α-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 α-actinin-2 preferential orientation in Z-disk. Last, we uncover FATZ-1 ability to phase-separate and form biomolecular condensates with α-actinin-2, raising the question whether FATZ proteins can create an interaction hub for Z-disk proteins through membraneless compartmentalization during myofibrillogenesis. American Association for the Advancement of Science 2021-05-28 /pmc/articles/PMC8163081/ /pubmed/34049882 http://dx.doi.org/10.1126/sciadv.abg7653 Text en 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). https://creativecommons.org/licenses/by-nc/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial license (https://creativecommons.org/licenses/by-nc/4.0/) , which permits use, distribution, and reproduction in any medium, so long as the resultant use is not for commercial advantage and provided the original work is properly cited.
spellingShingle Research Articles
Sponga, Antonio
Arolas, Joan L.
Schwarz, Thomas C.
Jeffries, Cy M.
Rodriguez Chamorro, Ariadna
Kostan, Julius
Ghisleni, Andrea
Drepper, Friedel
Polyansky, Anton
De Almeida Ribeiro, Euripedes
Pedron, Miriam
Zawadzka-Kazimierczuk, Anna
Mlynek, Georg
Peterbauer, Thomas
Doto, Pierantonio
Schreiner, Claudia
Hollerl, Eneda
Mateos, Borja
Geist, Leonhard
Faulkner, Georgine
Kozminski, Wiktor
Svergun, Dmitri I.
Warscheid, Bettina
Zagrovic, Bojan
Gautel, Mathias
Konrat, Robert
Djinović-Carugo, Kristina
Order from disorder in the sarcomere: FATZ forms a fuzzy but tight complex and phase-separated condensates with α-actinin
title Order from disorder in the sarcomere: FATZ forms a fuzzy but tight complex and phase-separated condensates with α-actinin
title_full Order from disorder in the sarcomere: FATZ forms a fuzzy but tight complex and phase-separated condensates with α-actinin
title_fullStr Order from disorder in the sarcomere: FATZ forms a fuzzy but tight complex and phase-separated condensates with α-actinin
title_full_unstemmed Order from disorder in the sarcomere: FATZ forms a fuzzy but tight complex and phase-separated condensates with α-actinin
title_short Order from disorder in the sarcomere: FATZ forms a fuzzy but tight complex and phase-separated condensates with α-actinin
title_sort order from disorder in the sarcomere: fatz forms a fuzzy but tight complex and phase-separated condensates with α-actinin
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8163081/
https://www.ncbi.nlm.nih.gov/pubmed/34049882
http://dx.doi.org/10.1126/sciadv.abg7653
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