Nucleotide-dependent farnesyl switch orchestrates polymerization and membrane binding of human guanylate-binding protein 1

Shydlovskyi S, Zienert AY, Ince S, Dovengerds C, Hohendahl A, Dargazanli JM, Blum A, Guenther SD, Kladt N, Stürzl M, Schauss AC, Kutsch M, Roux A, Praefcke GJK, Herrmann C (2017)

Publication Type: Journal article

Publication year: 2017

Journal

Proceedings of the National Academy of Sciences of the United States of America National Academy of Sciences

Book Volume: 114

Pages Range: E5559-E5568

Journal Issue: 28

DOI: 10.1073/pnas.1620959114

Abstract

Dynamin-like proteins (DLPs) mediate various membrane fusion and fission processes within the cell, which often require the polymerization of DLPs. An IFN-inducible family of DLPs, the guanylate-binding proteins (GBPs), is involved in antimicrobial and antiviral responses within the cell. Human guanylate-binding protein 1 (hGBP1), the founding member of GBPs, is also engaged in the regulation of cell adhesion and migration. Here, we show how the GTPase cycle of farnesylated hGBP1 (hGBP1F) regulates its self-assembly and membrane interaction. Using vesicles of various sizes as a lipid bilayer model, we show GTP-dependent membrane binding of hGBP1F In addition, we demonstrate nucleotide-dependent tethering ability of hGBP1F Furthermore, we report nucleotide-dependent polymerization of hGBP1F, which competes with membrane binding of the protein. Our results show that hGBP1F acts as a nucleotide-controlled molecular switch by modulating the accessibility of its farnesyl moiety, which does not require any supportive proteins.

Authors with CRIS profile

Michael Stürzl Professur für Molekulare und Experimentelle Chirurgie

Involved external institutions

Ruhr-Universität Bochum (RUB) DE Germany (DE) Universität zu Köln DE Germany (DE) University of Geneva / Université de Genève (UNIGE) CH Switzerland (CH)

How to cite

APA:

Shydlovskyi, S., Zienert, A.Y., Ince, S., Dovengerds, C., Hohendahl, A., Dargazanli, J.M.,... Herrmann, C. (2017). Nucleotide-dependent farnesyl switch orchestrates polymerization and membrane binding of human guanylate-binding protein 1. Proceedings of the National Academy of Sciences of the United States of America, 114(28), E5559-E5568. https://doi.org/10.1073/pnas.1620959114

MLA:

Shydlovskyi, Sergii, et al. "Nucleotide-dependent farnesyl switch orchestrates polymerization and membrane binding of human guanylate-binding protein 1." Proceedings of the National Academy of Sciences of the United States of America 114.28 (2017): E5559-E5568.

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