1. Order from disorder in the sarcomere: FATZ forms a fuzzy but tight complex and phase-separated condensates with α-actinin
- Author
-
Ariadna Rodriguez Chamorro, Andrea Ghisleni, Pierantonio Doto, Eneda Hollerl, Borja Mateos, Wiktor Kozminski, Robert Konrat, Kristina Djinović-Carugo, Miriam Pedron, Dmitri I. Svergun, Friedel Drepper, Anna Zawadzka-Kazimierczuk, Julius Kostan, Bettina Warscheid, Bojan Zagrovic, Georgine Faulkner, Claudia Schreiner, Joan L. Arolas, G. Mlynek, Euripedes de Almeida Ribeiro, Thomas Peterbauer, Cy M. Jeffries, Antonio Sponga, Leonhard Geist, Anton A. Polyansky, Mathias Gautel, and Thomas C. Schwarz
- Subjects
0303 health sciences ,Myofibril assembly ,Multidisciplinary ,Chemistry ,030302 biochemistry & molecular biology ,SciAdv r-articles ,macromolecular substances ,Compartmentalization (psychology) ,Filamin ,musculoskeletal system ,Sarcomere ,03 medical and health sciences ,Molecular recognition ,Structural Biology ,Biophysics ,ddc:500 ,Binding site ,Actin ,Function (biology) ,Research Articles ,030304 developmental biology ,Research Article - Abstract
Science advances 7(22), eabg7653 - (2021). doi:10.1126/sciadv.abg7653, 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., Published by Assoc., Washington, DC [u.a.]
- Published
- 2021