Journal Article

PUBDB-2021-02832

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Order from disorder in the sarcomere: FATZ forms a fuzzy but tight complex and phase-separated condensates with α-actinin

Sponga, A.Extern*EMBL* ; Arolas, J. L. ; Schwarz, T. C. ; Jeffries, C. M.EMBL* ; Rodriguez Chamorro, A. ; Kostan, J.Extern*EMBL* ; Ghisleni, A. ; Drepper, F. ; Polyansky, A. ; De Almeida Ribeiro, E. ; Pedron, M. ; Zawadzka-Kazimierczuk, A. ; Mlynek, G.Extern*EMBL* ; Peterbauer, T. ; Doto, P. ; Schreiner, C. ; Hollerl, E. ; Mateos, B. ; Geist, L. ; Faulkner, G. ; Kozminski, W. ; Svergun, D. I.EMBL* ; Warscheid, B. ; Zagrovic, B. ; Gautel, M. ; Konrat, R. ; Djinović-Carugo, K. (Corresponding author)

2021
Assoc. Washington, DC [u.a.]

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Please use a persistent id in citations: doi:10.1126/sciadv.abg7653  doi:10.3204/PUBDB-2021-02832

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.

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Contributing Institute(s):

1. EMBL-User (EMBL-User)
2. EMBL (EMBL)

Research Program(s):

1. 6G3 - PETRA III (DESY) (POF4-6G3) (POF4-6G3)
2. DFG project 390939984 - EXC 2189: CIBSS - Centre for Integrative Biological Signalling Studies (390939984) (390939984)

Experiment(s):

1. PETRA Beamline P12 (PETRA III)
2. PETRA Beamline P14 (PETRA III)

Appears in the scientific report 2021

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