S T R U C T U R A L B I O L O G Y

S C I E N T I F I C H I G H L I G H T S

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concentrations of α-actinin-2. Sarcomere assembly starts from punctate concentrates Z-bodies containing several Z-disc proteins including α-actinin-2, FATZ and actin. During sarcomere biogenesis, Z-bodies fuse together and associate with other proteins to form mature Z-disks. This process is reminiscent of membrane-less organelles.

Further research will investigate whether sarcomere biogenesis starts from biomolecular condensates, whereby FATZ proteins could act as scaffolds that locally concentrate partners essential for the initiation of myofibrillogenesis, leading to nucleation of cytoskeletal structures in muscle (Figure 44d).

PRINCIPAL PUBLICATION AND AUTHORS

Order from disorder in the sarcomere: FATZ forms a fuzzy but tight complex and phase-separated condensates with alpha-actinin, A. Sponga (a), J.L. Arolas (a), T.C. Schwarz (a), C.M. Jeffries (b), A. Rodriguez Chamorro (a), J. Kostan (a), A. Ghisleni (c), F. Drepper (d,e), A. Polyansky (a,f), E. De Almeida Ribeiro (a), M. Pedron (a), A. Zawadzka-Kazimierczuk (g), G. Mlynek (a), T. Peterbauer (h), Pierantonio Doto (a), C. Schreiner (a), E. Hollerl (a), B. Mateos (a), L. Geist (a), G. Faulkner (i), W. Kozminski (g), D.I. Svergun (c), B. Warscheid (d,e), B. Zagrovic (a), M. Gautel (c), R. Konrat (a), K. Djinović-Carugo (a,j), Sci. Adv. 7(22), eabg7653 (2021); https:/ www.doi.org/10.1126/sciadv.abg7653 (a) Department of Structural and Computational Biology, Max Perutz Labs, University of Vienna (Austria) (b) European Molecular Biology Laboratory (EMBL), Hamburg (Germany) (c) King s College London BHF Centre for Research Excellence, Randall Centre for Cell and Molecular Biophysics, London (UK) (d) Biochemistry and Functional Proteomics, Institute of Biology II, Faculty of Biology, University of Freiburg (Germany) (e) Signalling Research Centres BIOSS and CIBSS, University of Freiburg (Germany) (f) National Research University Higher School of Economics, Moscow (Russia) (g) Biological and Chemical Research Centre, Faculty of Chemistry, University of Warsaw (Poland) (h) Department of Biochemistry and Cell Biology, Max Perutz Labs, University of Vienna (Austria) (i) Department of Biology, University of Padova (Italy) (j) Department of Biochemistry, Faculty of Chemistry and Chemical Technology, University of Ljubljana (Slovenia)

REFERENCES

[1] A. Ribeiro Ede Jr. et al., Cell 159, 1447-1460 (2014). [2] N. Pinotsis et al., PNAS USA 117, 22101-22112 (2020). [3] T. Oda & H. Yanagisawa, Commun. Biol. 3, 585 (2020).

Fig. 44: a) Integrative model of α-actinin-2/FATZ-1 fuzzy complex displays a polar architecture with FATZ-1 bound on the concave side of the α-actinin-2 rod and stemming radially from LM anchoring points. b) Structural model of the α-actinin-2/FATZ-1 assembly bound to F-actin in the Z-disk. c) Differential interference contrast/fluorescence images of FATZ-1-GFP mixed with Cy5-labelled rod-actinin-2,

revealing enrichment of actinin-2 inside FATZ-1 condensates. d) Proposed mechanism of sarcomere biogenesis starting from FATZ-1 condensates, whereby FATZ-1 acts as a scaffold that nucleates other core (client) Z-disk partners essential for the formation of Z-bodies.