TY  - JOUR
AU  - Sponga, Antonio
AU  - Arolas, Joan L.
AU  - Schwarz, Thomas C.
AU  - Jeffries, Cy M.
AU  - Rodriguez Chamorro, Ariadna
AU  - Kostan, Julius
AU  - Ghisleni, Andrea
AU  - Drepper, Friedel
AU  - Polyansky, Anton
AU  - De Almeida Ribeiro, Euripedes
AU  - Pedron, Miriam
AU  - Zawadzka-Kazimierczuk, Anna
AU  - Mlynek, Georg
AU  - Peterbauer, Thomas
AU  - Doto, Pierantonio
AU  - Schreiner, Claudia
AU  - Hollerl, Eneda
AU  - Mateos, Borja
AU  - Geist, Leonhard
AU  - Faulkner, Georgine
AU  - Kozminski, Wiktor
AU  - Svergun, Dmitri I.
AU  - Warscheid, Bettina
AU  - Zagrovic, Bojan
AU  - Gautel, Mathias
AU  - Konrat, Robert
AU  - Djinović-Carugo, Kristina
TI  - Order from disorder in the sarcomere: FATZ forms a fuzzy but tight complex and phase-separated condensates with α-actinin
JO  - Science advances
VL  - 7
IS  - 22
SN  - 2375-2548
CY  - Washington, DC [u.a.]
PB  - Assoc.
M1  - PUBDB-2021-02832
SP  - eabg7653 -
PY  - 2021
AB  - 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.
LB  - PUB:(DE-HGF)16
C6  - pmid:34049882
UR  - <Go to ISI:>//WOS:000655906900037
DO  - DOI:10.1126/sciadv.abg7653
UR  - https://bib-pubdb1.desy.de/record/459946
ER  -