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Ca2+-independent binding of an EF-hand domain to a novel motif in the α-actinin–titin complex

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Abstract

The interaction between α-actinin and titin, two modular muscle proteins, is essential for sarcomere assembly. We have solved the solution structure of a complex between the calcium-insensitive C-terminal EF-hand domain of α-actinin-2 and the seventh Z-repeat of titin. The structure of the complex is in a semi-open conformation and closely resembles that of myosin light chains in their complexes with heavy chain IQ motifs. However, no IQ motif is present in the Z-repeat, suggesting that the semi-open conformation is a general structural solution for calcium-independent recognition of EF-hand domains.

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Figure 1: Structure of the complex of α-actinin-2 Act-EF34 with titin Zr7.
Figure 2: Comparison of the secondary and tertiary structure of Act-EF34 with other EF-hands.
Figure 3: Analysis of the binding motif of Zr7 with that of IQ motifs and other Z-repeats.
Figure 4: Comparison of the structure of the complex of α-actinin-2 Act-EF34–titin Zr7 with those of other representative EF-hand domain complexes.

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Acknowledgements

The authors wish to thank G. Stier for help in protein production at the early stage of the project, and R. Biekofsky and J. Feeney for helpful discussions. The National 800 MHz NMR facility in Cambridge is supported by the BBSRC and the Wellcome Trust. This work is dedicated to the memory of Matti Saraste.

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Authors and Affiliations

  1. Division of Molecular Structure, National Institute for Medical Research, The Ridgeway, Mill Hill, London, NW7 1AA, UK

    R. Andrew Atkinson, Catherine Joseph & Annalisa Pastore

  2. MRC Biomedical NMR Centre, National Institute for Medical Research, The Ridgeway, Mill Hill, London, NW7 1AA, UK

    Geoff Kelly, Frederick W. Muskett & Thomas A. Frenkiel

  3. Department of Biochemistry, University of Cambridge, 80 Tennis Court Road, Old Addenbrookes Site, Cambridge, CB2 1GA, UK

    Daniel Nietlispach

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  1. R. Andrew Atkinson
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  2. Catherine Joseph
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  7. Annalisa Pastore
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Correspondence to Annalisa Pastore.

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Atkinson, R., Joseph, C., Kelly, G. et al. Ca2+-independent binding of an EF-hand domain to a novel motif in the α-actinin–titin complex. Nat Struct Mol Biol 8, 853–857 (2001). https://doi.org/10.1038/nsb1001-853

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