King's College London

Research portal

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

Research output: Contribution to journalArticlepeer-review

Antonio Sponga, Joan L. Arolas, Thomas C. Schwarz, Cy M. Jeffries, Ariadna Rodriguez Chamorro, Julius Kostan, Andrea Ghisleni, Friedel Drepper, Anton Polyansky, Euripedes de Almeida Ribeiro, Miriam Pedron, Anna Zawadzka-Kazimierczuk, Georg Mlynek, Thomas Peterbauer, Pierantonio Doto, Claudia Schreiner, Eneda Hollerl, Borja Mateos, Leonhard Geist, Georgine Faulkner & 7 more Wiktor Kozminski, Dmitri I. Svergun, Bettina Warscheid, Bojan Zagrovic, Mathias Gautel, Robert Konrat, Kristina Djinović-Carugo

Original languageEnglish
Article numbereabg7653
JournalScience Advances
Issue number22
Published28 May 2021

Bibliographical note

Funding Information: K.D.-C.'s research was supported by a Marie Curie Initial Training Network: MUZIC (no. 238423); Austrian Science Fund (FWF) Projects I525, I1593, P22276, P19060, and W1221; Federal Ministry of Economy, Family, and Youth through the initiative ?Laura Bassi Centres of Expertise,? funding the Centre of Optimized Structural Studies, no. 253275; the Wellcome Trust Collaborative Award (201543/Z/16); COST action BM1405-Non-globular proteins from sequence to structure, function and application in molecular physiopathology (NGP-NET); WWTF (Vienna Science and Technology Fund) Chemical Biology project LS17-008; Christian Doppler Laboratory for High-Content Structural Biology and Biotechnology; and the Austrian-Slovak Interreg Project B301 StruBioMol, University of Vienna Research Platform Comammox and by the University of Vienna. The work was supported by the Austrian Science Fund FWF grant P30550 to B.Z. M.G. and A.G. were supported by the Wellcome Trust Collaborative Award (201543/Z/16). M.G. holds the British Heart Foundation Chair of Molecular Cardiology. This work was supported by a grant from the Polish National Science Centre to W.K. (MAESTRO, 2015/18/A/ST4/00270). Research in B.W.'s laboratory was supported by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) research FOR 2743, Project ID 403222702/SFB 1381, and Germany's Excellence Strategy (CIBSS-EXC-2189-Project ID 390939984). D.I.S. and C.M.J. acknowledge the support of the European Union's Horizon 2020 research and innovation programme ?iNEXT Discovery? grant agreement no. 871037. Publisher 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). Copyright: Copyright 2021 Elsevier B.V., All rights reserved.

King's Authors


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.

View graph of relations

© 2020 King's College London | Strand | London WC2R 2LS | England | United Kingdom | Tel +44 (0)20 7836 5454