title: Mechanism of GTPase-activity-induced self-assembly of human guanylate binding protein 1.
abstract: Human guanylate binding protein 1 (hGBP1) belongs to the dynamin superfamily of large GTPases (LGs). In the course of GTP hydrolysis, the protein undergoes structural changes leading to self-assembly of the protein, which is a characteristic property of all family members. For self-assembly, the protein employs two distinct interaction sites, one of which is located within the LG domain of the protein located at the N-terminus, and the second is located in the C-terminal alpha-helical domain. Here, we identify intramolecular contacts between the LG domain and the helical part of hGBP1, which relay nucleotide-dependent structural changes from the N-terminus to the C-terminus and thereby mediate tetramer formation of the protein through a second contact site at the C-terminus. Furthermore, we demonstrate the impact of this intramolecular communication on the enzymatic activity of hGBP1 and on its cellular localization.
authors.affiliation: Physical Chemistry I, Faculty of Chemistry and Biochemistry, Ruhr University Bochum, Universitaetsstr. 150, 44780 Bochum, Germany.
authors.forename: Tobias
authors.initials: T
authors.lastname: Vöpel
authors.forename: Adrian
authors.initials: A
authors.lastname: Syguda
authors.forename: Nathalie
authors.initials: N
authors.lastname: Britzen-Laurent
authors.forename: Simone
authors.initials: S
authors.lastname: Kunzelmann
authors.forename: Maik-Borris
authors.initials: MB
authors.lastname: Lüdemann
authors.forename: Christine
authors.initials: C
authors.lastname: Dovengerds
authors.forename: Michael
authors.initials: M
authors.lastname: Stürzl
authors.forename: Christian
authors.initials: C
authors.lastname: Herrmann
mesh_terms: D001665:Binding Sites; D018360:Crystallography, X-Ray; D020558:GTP Phosphohydrolases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D019204:GTP-Binding Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D016297:Mutagenesis, Site-Directed; D009711:Nucleotides / Q000378:metabolism; D011485:Protein Binding; D020836:Protein Structure, Quaternary; D017434:Protein Structure, Tertiary
chemical_list: C490287:GBP1 protein, human; D009711:Nucleotides; D020558:GTP Phosphohydrolases; D019204:GTP-Binding Proteins