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Magic angle spinning NMR structure of human cofilin-2 assembled on actin filaments reveals isoform-specific conformation and binding mode

Author

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  • Jodi Kraus

    (University of Delaware
    Princeton University)

  • Ryan W. Russell

    (University of Delaware)

  • Elena Kudryashova

    (The Ohio State University)

  • Chaoyi Xu

    (University of Delaware)

  • Nidhi Katyal

    (University of Delaware)

  • Juan R. Perilla

    (University of Delaware)

  • Dmitri S. Kudryashov

    (The Ohio State University)

  • Tatyana Polenova

    (University of Delaware)

Abstract

Actin polymerization dynamics regulated by actin-binding proteins are essential for various cellular functions. The cofilin family of proteins are potent regulators of actin severing and filament disassembly. The structural basis for cofilin-isoform-specific severing activity is poorly understood as their high-resolution structures in complex with filamentous actin (F-actin) are lacking. Here, we present the atomic-resolution structure of the muscle-tissue-specific isoform, cofilin-2 (CFL2), assembled on ADP-F-actin, determined by magic-angle-spinning (MAS) NMR spectroscopy and data-guided molecular dynamics (MD) simulations. We observe an isoform-specific conformation for CFL2. This conformation is the result of a unique network of hydrogen bonding interactions within the α2 helix containing the non-conserved residue, Q26. Our results indicate F-site interactions that are specific between CFL2 and ADP-F-actin, revealing mechanistic insights into isoform-dependent F-actin disassembly.

Suggested Citation

  • Jodi Kraus & Ryan W. Russell & Elena Kudryashova & Chaoyi Xu & Nidhi Katyal & Juan R. Perilla & Dmitri S. Kudryashov & Tatyana Polenova, 2022. "Magic angle spinning NMR structure of human cofilin-2 assembled on actin filaments reveals isoform-specific conformation and binding mode," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-29595-9
    DOI: 10.1038/s41467-022-29595-9
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    References listed on IDEAS

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    1. Wenyu Sun & Ya-Xiang Yuan, 2006. "Optimization Theory and Methods," Springer Optimization and Its Applications, Springer, number 978-0-387-24976-6, June.
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    Cited by:

    1. Alexander J. Bryer & Juan S. Rey & Juan R. Perilla, 2023. "Performance efficient macromolecular mechanics via sub-nanometer shape based coarse graining," Nature Communications, Nature, vol. 14(1), pages 1-19, December.

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