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Characterization of a fold in TANGO1 evolved from SH3 domains for the export of bulky cargos

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  • Oliver Arnolds

    (Ruhr University of Bochum
    Karolinska University Hospital)

  • Raphael Stoll

    (Ruhr University of Bochum)

Abstract

Bulky cargos like procollagens, apolipoproteins, and mucins exceed the size of conventional COPII vesicles. During evolution a process emerged in metazoans, predominantly governed by the TANGO1 protein family, that organizes cargo at the exit sites of the endoplasmic reticulum and facilitates export by the formation of tunnel-like connections between the ER and Golgi. Hitherto, cargo-recognition appeared to be mediated by an SH3-like domain. Based on structural and dynamic data as well as interaction studies from NMR spectroscopy and microscale thermophoresis presented here, we show that the luminal cargo-recognition domain of TANGO1 adopts a new functional fold for which we suggest the term MOTH (MIA, Otoraplin, TALI/TANGO1 homology) domain. These MOTH domains, as well as an evolutionary intermediate found in invertebrates, constitute a distinct domain family that emerged from SH3 domains and acquired the ability to bind collagen.

Suggested Citation

  • Oliver Arnolds & Raphael Stoll, 2023. "Characterization of a fold in TANGO1 evolved from SH3 domains for the export of bulky cargos," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-37705-4
    DOI: 10.1038/s41467-023-37705-4
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    1. Kathryn Tunyasuvunakool & Jonas Adler & Zachary Wu & Tim Green & Michal Zielinski & Augustin Žídek & Alex Bridgland & Andrew Cowie & Clemens Meyer & Agata Laydon & Sameer Velankar & Gerard J. Kleywegt, 2021. "Highly accurate protein structure prediction for the human proteome," Nature, Nature, vol. 596(7873), pages 590-596, August.
    2. John Jumper & Richard Evans & Alexander Pritzel & Tim Green & Michael Figurnov & Olaf Ronneberger & Kathryn Tunyasuvunakool & Russ Bates & Augustin Žídek & Anna Potapenko & Alex Bridgland & Clemens Me, 2021. "Highly accurate protein structure prediction with AlphaFold," Nature, Nature, vol. 596(7873), pages 583-589, August.
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    1. Ishier Raote & Ann-Helen Rosendahl & Hanna-Maria Häkkinen & Carina Vibe & Ismail Küçükaylak & Mugdha Sawant & Lena Keufgens & Pia Frommelt & Kai Halwas & Katrina Broadbent & Marina Cunquero & Gustavo , 2024. "TANGO1 inhibitors reduce collagen secretion and limit tissue scarring," Nature Communications, Nature, vol. 15(1), pages 1-12, December.

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