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

Article Article scientifique Article Nucleotide-dependent farnesyl switch orchestrates polymerization and membrane binding of human guanylate-binding protein 1 eng 2017 author Shydlovskyi Sergii author Zienert Anke Y. author Ince Semra author Dovengerds Christine author Hohendahl Annika 740692 author Dargazanli Julia M. author Blum Ailisa author Günther Saskia D. author Kladt Nikolay author Stürzl Michael author Schauss Astrid C. author Kutsch Miriam 861223 author Roux Aurélien 0000-0002-6088-0711 716946 author Praefcke Gerrit J. K. author Herrmann Christian E5559-E5568 10.1073/pnas.1620959114 0027-8424 http://www.pnas.org/lookup/doi/10.1073/pnas.1620959114 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. Dewey 540 39 Département de biochimie 144 false Proceedings of the National Academy of Sciences 114 28 81b3082d-456e-4728-816c-4dbd9e8fd643 Article (Published version) Restricted Nucleotide_AR_17.pdf 1874604 application/pdf restrictedAccess Faculté des sciences / Section de chimie et biochimie / Département de biochimie

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Nucleotide-dependent farnesyl switch orchestrates polymerization and membrane binding of human guanylate-binding protein 1	Proceedings of the National Academy of Sciences			2017	315	0

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Kutsch, Miriam