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

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • 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

Published Date

  • July 2017

Published In

Volume / Issue

  • 114 / 28

Start / End Page

  • E5559 - E5568

PubMed ID

  • 28645896

Pubmed Central ID

  • PMC5514708

Electronic International Standard Serial Number (EISSN)

  • 1091-6490

International Standard Serial Number (ISSN)

  • 0027-8424

Digital Object Identifier (DOI)

  • 10.1073/pnas.1620959114


  • eng