Shydlovskyi, Sergii, Zienert, Anke Y., Ince, Semra, Dovengerds, Christine, Hohendahl, Annika, Dargazanli, Julia M., Blum, Ailisa ORCID: 0000-0003-4666-9255, Guenther, Saskia D., Kladt, Nikolay, Stuerzl, Michael, Schauss, Astrid C., Kutsch, Miriam ORCID: 0000-0002-9346-2196, Roux, Aurelien, Praefcke, Gerrit J. K. and Herrmann, Christian (2017). Nucleotide-dependent farnesyl switch orchestrates polymerization and membrane binding of human guanylate-binding protein 1. Proc. Natl. Acad. Sci. U. S. A., 114 (28). S. E5559 - 10. WASHINGTON: NATL ACAD SCIENCES. ISSN 0027-8424

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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.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Shydlovskyi, SergiiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Zienert, Anke Y.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ince, SemraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Dovengerds, ChristineUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hohendahl, AnnikaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Dargazanli, Julia M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Blum, AilisaUNSPECIFIEDorcid.org/0000-0003-4666-9255UNSPECIFIED
Guenther, Saskia D.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kladt, NikolayUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Stuerzl, MichaelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schauss, Astrid C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kutsch, MiriamUNSPECIFIEDorcid.org/0000-0002-9346-2196UNSPECIFIED
Roux, AurelienUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Praefcke, Gerrit J. K.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Herrmann, ChristianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-225039
DOI: 10.1073/pnas.1620959114
Journal or Publication Title: Proc. Natl. Acad. Sci. U. S. A.
Volume: 114
Number: 28
Page Range: S. E5559 - 10
Date: 2017
Publisher: NATL ACAD SCIENCES
Place of Publication: WASHINGTON
ISSN: 0027-8424
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
INTERFERON-INDUCIBLE GTPASES; GTP HYDROLYSIS; DYNAMIN SUPERFAMILY; ANTIVIRAL ACTIVITY; GAMMA; HGBP1; FUSION; MACROPHAGES; FISSION; GMPMultiple languages
Multidisciplinary SciencesMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/22503

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