title: Invited review: MnmE, a GTPase that drives a complex tRNA modification reaction.
abstract: MnmE is a multi-domain GTPase that is conserved from bacteria to man. Together with its partner protein MnmG it is involved in the synthesis of a tRNA wobble uridine modification. The orthologues of these proteins in eukaryotes are targeted to mitochondria and mutations in the encoding genes are associated with severe mitochondrial diseases. While classical small GTP-binding proteins are regulated via auxiliary GEFs and GAPs, the GTPase activity of MnmE is activated via potassium-dependent homodimerization of its G domains. In this review we focus on the catalytic mechanism of GTP hydrolysis by MnmE and the large scale conformational changes that are triggered throughout the GTPase cycle. We also discuss how these conformational changes might be used to drive and tune the complex tRNA modification reaction. © 2016 Wiley Periodicals, Inc. Biopolymers 105: 568-579, 2016.
authors.affiliation: Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY, 10032.|Howard Hughes Medical Institute, Columbia University, New York, NY, 10032.
authors.forename: Marcus
authors.initials: M
authors.lastname: Fislage
authors.affiliation: Department of Cell Biochemistry, University of Groningen, Nijenborgh 7, Groningen, 9747 AG, Netherlands.|Structural Biology Brussels, Vrije Universiteit Brussel, Pleinlaan 2, Brussel, 1050, Belgium.|Structural Biology Research Center, VIB, Pleinlaan 2, Brussel, 1050, Belgium.
authors.forename: Lina
authors.initials: L
authors.lastname: Wauters
authors.affiliation: Structural Biology Brussels, Vrije Universiteit Brussel, Pleinlaan 2, Brussel, 1050, Belgium.|Structural Biology Research Center, VIB, Pleinlaan 2, Brussel, 1050, Belgium.
authors.forename: Wim
authors.initials: W
authors.lastname: Versées
mesh_terms: D000818:Animals; D020558:GTP Phosphohydrolases / Q000235:genetics / Q000378:metabolism; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics / Q000378:metabolism; D006801:Humans; D046912:Multiprotein Complexes / Q000235:genetics / Q000378:metabolism; D000072417:Protein Domains; D012323:RNA Processing, Post-Transcriptional / Q000502:physiology*; D012343:RNA, Transfer / Q000235:genetics / Q000378:metabolism
chemical_list: D020662:Guanine Nucleotide Exchange Factors; D046912:Multiprotein Complexes; D012343:RNA, Transfer; D020558:GTP Phosphohydrolases
keywords: G proteins activated by dimerization; GTPase; MnmE; MnmG; tRNA modification