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

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dc.abstract.enIn 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.
dc.affiliationUniwersytet Warszawski
dc.contributor.authorKoźmiński, Wiktor
dc.contributor.authorChamorro, Ariadna Rodriguez
dc.contributor.authorKostan, Julius
dc.contributor.authorGhisleni, Andrea
dc.contributor.authorDrepper, Friedel
dc.contributor.authorPolyansky, Anton
dc.contributor.authorRibeiro, Euripedes De Almeida
dc.contributor.authorSponga, Antonio
dc.contributor.authorArolas, Joan L.
dc.contributor.authorSchwarz, Thomas C.
dc.contributor.authorJeffries, Cy M.
dc.contributor.authorPeterbauer, Thomas
dc.contributor.authorDoto, Pierantonio
dc.contributor.authorSchreiner, Claudia
dc.contributor.authorZawadzka-Kazimierczuk, Anna
dc.contributor.authorPedron, Miriam
dc.contributor.authorMlynek, Georg
dc.contributor.authorWarscheid, Bettina
dc.contributor.authorZagrovic, Bojan
dc.contributor.authorGautel, Mathias
dc.contributor.authorKonrat, Robert
dc.contributor.authorDjinović-Carugo, Kristina
dc.contributor.authorHollerl, Eneda
dc.contributor.authorMateos, Borja
dc.contributor.authorGeist, Leonhard
dc.contributor.authorFaulkner, Georgine
dc.contributor.authorSvergun, Dmitri I.
dc.date.accessioned2024-01-25T16:09:10Z
dc.date.available2024-01-25T16:09:10Z
dc.date.copyright2021-05-28
dc.date.issued2021
dc.description.accesstimeAT_PUBLICATION
dc.description.financePublikacja bezkosztowa
dc.description.number22
dc.description.versionFINAL_PUBLISHED
dc.description.volume7
dc.identifier.doi10.1126/SCIADV.ABG7653
dc.identifier.urihttps://repozytorium.uw.edu.pl//handle/item/115033
dc.identifier.weblinkhttps://syndication.highwire.org/content/doi/10.1126/sciadv.abg7653
dc.languageeng
dc.pbn.affiliationchemical sciences
dc.relation.ispartofScience Advances
dc.relation.pageseabg7653
dc.rightsCC-BY-NC
dc.sciencecloudnosend
dc.titleOrder from disorder in the sarcomere: FATZ forms a fuzzy but tight complex and phase-separated condensates with α-actinin
dc.typeJournalArticle
dspace.entity.typePublication