Nucleotide-dependent farnesyl switch orchestrates polymerization and membrane binding of human guanylate-binding protein 1.
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.
Shydlovskyi, S; Zienert, AY; Ince, S; Dovengerds, C; Hohendahl, A; Dargazanli, JM; Blum, A; Günther, SD; Kladt, N; Stürzl, M; Schauss, AC; Kutsch, M; Roux, A; Praefcke, GJK; Herrmann, C
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