7A8U

Crystal structure of sarcomeric protein FATZ-1 (d91-FATZ-1 construct) in complex with rod domain of alpha-actinin-2

Summary for 7A8U

• Entry DOI: 10.2210/pdb7a8u/pdb
• Related: 7A8T 7ANK
• Descriptor: Alpha-actinin-2, Myozenin-1 (2 entities in total)
• Functional Keywords: z-disk complex, f-actin crosslinking protein, scaffolding protein, fuzzy complex, structural protein
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 2
• Total formula weight: 77735.98

Authors

Sponga, A.,Arolas, J.L.,Rodriguez Chamorro, A.,Mlynek, G.,Hollerl, E.,Schreiner, C.,Pedron, M.,Kostan, J.,Ribeiro, E.A.,Djinovic-Carugo, K. (deposition date: 2020-08-31, release date: 2021-06-30, Last modification date: 2024-01-31)

Primary citation

Sponga, A.,Arolas, J.L.,Schwarz, T.C.,Jeffries, C.M.,Rodriguez Chamorro, A.,Kostan, J.,Ghisleni, A.,Drepper, F.,Polyansky, A.,De Almeida Ribeiro, E.,Pedron, M.,Zawadzka-Kazimierczuk, A.,Mlynek, G.,Peterbauer, T.,Doto, P.,Schreiner, C.,Hollerl, E.,Mateos, B.,Geist, L.,Faulkner, G.,Kozminski, W.,Svergun, D.I.,Warscheid, B.,Zagrovic, B.,Gautel, M.,Konrat, R.,Djinovic-Carugo, K.
Order from disorder in the sarcomere: FATZ forms a fuzzy but tight complex and phase-separated condensates with alpha-actinin.
Sci Adv, 7:-, 2021

PubMed 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.

PubMed: 34049882
DOI: 10.1126/sciadv.abg7653

Experimental method

X-RAY DIFFRACTION (3.802 Å)