title: Structure of a SMG8-SMG9 complex identifies a G-domain heterodimer in the NMD effector proteins.
abstract: Nonsense-mediated mRNA decay (NMD) is a eukaryotic mRNA degradation pathway involved in surveillance and post-transcriptional regulation, and executed by the concerted action of severaltrans-acting factors. The SMG1 kinase is an essential NMD factor in metazoans and is associated with two recently identified and yet poorly characterized proteins, SMG8 and SMG9. We determined the 2.5 Å resolution crystal structure of a SMG8-SMG9 core complex fromC. elegansWe found that SMG8-SMG9 is a G-domain heterodimer with architectural similarities to the dynamin-like family of GTPases such as Atlastin and GBP1. The SMG8-SMG9 heterodimer forms in the absence of nucleotides, with interactions conserved from worms to humans. Nucleotide binding occurs at the G domain of SMG9 but not of SMG8. Fitting the GDP-bound SMG8-SMG9 structure in EM densities of the human SMG1-SMG8-SMG9 complex raises the possibility that the nucleotide site of SMG9 faces SMG1 and could impact the kinase conformation and/or regulation.
authors.affiliation: Department of Structural Cell Biology, Max-Planck-Institute of Biochemistry, D-82152 Martinsried, Germany.
authors.forename: Liang
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Structural Cell Biology, Max-Planck-Institute of Biochemistry, D-82152 Martinsried, Germany.
authors.forename: Mahesh
authors.initials: M
authors.lastname: Lingaraju
authors.affiliation: Department of Structural Cell Biology, Max-Planck-Institute of Biochemistry, D-82152 Martinsried, Germany.
authors.forename: Claire
authors.initials: C
authors.lastname: Basquin
authors.affiliation: Department of Structural Cell Biology, Max-Planck-Institute of Biochemistry, D-82152 Martinsried, Germany.
authors.forename: Jérome
authors.initials: J
authors.lastname: Basquin
authors.affiliation: Department of Structural Cell Biology, Max-Planck-Institute of Biochemistry, D-82152 Martinsried, Germany conti@biochem.mpg.de.
authors.forename: Elena
authors.initials: E
authors.lastname: Conti
mesh_terms: D000818:Animals; D001665:Binding Sites; D017173:Caenorhabditis elegans / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000737:chemistry* / Q000378:metabolism*; D018360:Crystallography, X-Ray; D008958:Models, Molecular; D059365:Nonsense Mediated mRNA Decay; D011485:Protein Binding; D000072417:Protein Domains; D055503:Protein Multimerization; D017346:Protein Serine-Threonine Kinases / Q000737:chemistry / Q000378:metabolism; D012323:RNA Processing, Post-Transcriptional; D012333:RNA, Messenger
chemical_list: D029742:Caenorhabditis elegans Proteins; D012333:RNA, Messenger; C581743:SMG-8 protein, C elegans; C000622670:SMG-9 protein, C elegans; D017346:Protein Serine-Threonine Kinases; C490966:SMG-1 protein, C elegans
keywords: C. elegans; G domain; NMD; post-transcriptional regulation