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The structure of the actin filament uncapping complex mediated by twinfilin.

<div class='caption-title'>The twinfilin/CP/actin complex.</div>
<div class='caption-title'>Binary interactions in the twinfilin/CP/actin complex.</div>
<div class='caption-title'>Conformations of CP.</div>
Mwangangi DM, Manser E, Robinson RC
OpenAccess logo Sci Adv 7 (2021)
Cited: 15 times
EuropePMC logo PMID: 33571120

Abstract

Uncapping of actin filaments is essential for driving polymerization and depolymerization dynamics from capping protein-associated filaments; however, the mechanisms of uncapping leading to rapid disassembly are unknown. Here, we elucidated the x-ray crystal structure of the actin/twinfilin/capping protein complex to address the mechanisms of twinfilin uncapping of actin filaments. The twinfilin/capping protein complex binds to two G-actin subunits in an orientation that resembles the actin filament barbed end. This suggests an unanticipated mechanism by which twinfilin disrupts the stable capping of actin filaments by inducing a G-actin conformation in the two terminal actin subunits. Furthermore, twinfilin disorders critical actin-capping protein interactions, which will assist in the dissociation of capping protein, and may promote filament uncapping through a second mechanism involving V-1 competition for an actin-binding surface on capping protein. The extensive interactions with capping protein indicate that the evolutionary conserved role of twinfilin is to uncap actin filaments.

Articles - 7ccc mentioned but not cited (1)

  1. Computational study of the impact of nucleotide variations on highly conserved proteins: In the case of actin. Duong HTT, Suzuki H, Katagiri S, Shibata M, Arai M, Yura K. Biophys Physicobiol 19 e190025 (2022)


Reviews citing this publication (4)

  1. Biochemical and mechanical regulation of actin dynamics. Lappalainen P, Kotila T, Jégou A, Romet-Lemonne G. Nat Rev Mol Cell Biol 23 836-852 (2022)
  2. Actin-Associated Proteins and Small Molecules Targeting the Actin Cytoskeleton. Gao J, Nakamura F. Int J Mol Sci 23 2118 (2022)
  3. The dynamic instability of actin filament barbed ends. Romet-Lemonne G, Jégou A. J Cell Biol 220 e202102020 (2021)
  4. Mechanisms of actin disassembly and turnover. Goode BL, Eskin J, Shekhar S. J Cell Biol 222 e202309021 (2023)

Articles citing this publication (10)

  1. A barbed end interference mechanism reveals how capping protein promotes nucleation in branched actin networks. Funk J, Merino F, Schaks M, Rottner K, Raunser S, Bieling P. Nat Commun 12 5329 (2021)
  2. The dynein light chain protein Tda2 functions as a dimerization engine to regulate actin capping protein during endocytosis. Lamb AK, Fernandez AN, Peersen OB, Di Pietro SM. Mol Biol Cell 32 1459-1473 (2021)
  3. Actin capping protein regulates postsynaptic spine development through CPI-motif interactions. Myers KR, Fan Y, McConnell P, Cooper JA, Zheng JQ. Front Mol Neurosci 15 1020949 (2022)
  4. Nuclear Actin Polymerization Regulates Cell Epithelial-Mesenchymal Transition. Du WW, Qadir J, Du KY, Chen Y, Wu N, Yang BB. Adv Sci (Weinh) 10 e2300425 (2023)
  5. Structural and biochemical evidence for the emergence of a calcium-regulated actin cytoskeleton prior to eukaryogenesis. Akıl C, Tran LT, Orhant-Prioux M, Baskaran Y, Senju Y, Takeda S, Chotchuang P, Muengsaen D, Schulte A, Manser E, Blanchoin L, Robinson RC. Commun Biol 5 890 (2022)
  6. Structural basis of rapid actin dynamics in the evolutionarily divergent Leishmania parasite. Kotila T, Wioland H, Selvaraj M, Kogan K, Antenucci L, Jégou A, Huiskonen JT, Romet-Lemonne G, Lappalainen P. Nat Commun 13 3442 (2022)
  7. Structure and function of an atypical homodimeric actin capping protein from the malaria parasite. Bendes ÁÁ, Kursula P, Kursula I. Cell Mol Life Sci 79 125 (2022)
  8. Cross-Platform Synaptic Network Analysis of Human Entorhinal Cortex Identifies TWF2 as a Modulator of Dendritic Spine Length. Walker CK, Greathouse KM, Tuscher JJ, Dammer EB, Weber AJ, Liu E, Curtis KA, Boros BD, Freeman CD, Seo JV, Ramdas R, Hurst C, Duong DM, Gearing M, Murchison CF, Day JJ, Seyfried NT, Herskowitz JH. J Neurosci 43 3764-3785 (2023)
  9. Mechanism of actin capping protein recruitment and turnover during clathrin-mediated endocytosis. Lamb AK, Fernandez AN, Eadaim A, Johnson K, Di Pietro SM. J Cell Biol 223 e202306154 (2024)
  10. Multicomponent regulation of actin barbed end assembly by twinfilin, formin and capping protein. Ulrichs H, Gaska I, Shekhar S. Nat Commun 14 3981 (2023)


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