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 guan...

Full description

Saved in:
Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2017-07, Vol.114 (28), p.E5559-E5568
Main Authors: Shydlovskyi, Sergii, Zienert, Anke Y., Ince, Semra, Dovengerds, Christine, Hohendahl, Annika, Dargazanli, Julia M., Blum, Ailisa, Günther, Saskia D., Kladt, Nikolay, Stürzl, Michael, Schauss, Astrid C., Kutsch, Miriam, Roux, Aurélien, Praefcke, Gerrit J. K., Herrmann, Christian
Format: Article
Language:English
Subjects:
Binding Sites
Biological Sciences
Catalysis
Cell adhesion
Cell Membrane - metabolism
Dynamin
GTP Phosphohydrolases - metabolism
GTP-Binding Proteins - metabolism
Guanosine 5'-O-(3-Thiotriphosphate) - metabolism
Guanosine triphosphatases
Guanosine triphosphate
Guanosine Triphosphate - chemistry
Guanylate-binding protein
HeLa Cells
Humans
Hydrolysis
Immunity, Innate
Interferon
Liposomes - chemistry
Membrane fusion
Membrane proteins
Membrane vesicles
Membranes
Microscopy, Electron
Molecular machines
Organic chemicals
PNAS Plus
Polymerization
Polymers - chemistry
Prenylation
Protein Binding
Proteins
Self-assembly
Tethering
Citations: Items that this one cites
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.1620959114