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

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 FaulknerWiktor Kozminski, Dmitri I. Svergun, Bettina Warscheid, Bojan Zagrovic, Mathias Gautel, Robert Konrat, Kristina Djinović-Carugo*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

13 Citations (Scopus)

Abstract

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.

Original languageEnglish
Article numbereabg7653
JournalScience Advances
Volume7
Issue number22
DOIs
Publication statusPublished - 28 May 2021

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