title: Domain organization within the nuclear export factor Mex67:Mtr2 generates an extended mRNA binding surface.
abstract: The Mex67:Mtr2 complex is the principal yeast nuclear export factor for bulk mRNA and also contributes to ribosomal subunit export. Mex67 is a modular protein constructed from four domains (RRM, LRR, NTF2-like and UBA) that have been thought to be joined by flexible linkers like beads on a string, with the RRM and LRR domains binding RNAs and the NTF2-like and UBA domains binding FG-nucleoporins to facilitate movement through nuclear pores. Here, we show that the NTF2-like domain from Saccharomyces cerevisiae Mex67:Mtr2 also contributes to RNA binding. Moreover, the 3.3 Å resolution crystal structure of the Mex67(ΔUBA):Mtr2 complex, supplemented with small angle X-ray scattering data, indicated that the LRR domain has a defined spatial relationship to the Mex67(NTF2L):Mtr2 region. Conversely, the RRM domain and especially the UBA domain are more mobile. The conformation assumed by the LRR and NTF2-like domains results in clusters of positively-charged residues on each becoming arranged to form a continuous interface for binding RNA on the opposite side of the complex to the region that interacts with FG-nucleoporins to facilitate passage through nuclear pores.
authors.affiliation: MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge Biomedical Campus, Cambridge CB2 0QH, UK.
authors.forename: Shintaro
authors.initials: S
authors.lastname: Aibara
authors.affiliation: MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge Biomedical Campus, Cambridge CB2 0QH, UK.
authors.forename: Eugene
authors.initials: E
authors.lastname: Valkov
authors.affiliation: MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge Biomedical Campus, Cambridge CB2 0QH, UK.
authors.forename: Meindert
authors.initials: M
authors.lastname: Lamers
authors.affiliation: MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge Biomedical Campus, Cambridge CB2 0QH, UK ms@mrc-lmb.cam.ac.uk.
authors.forename: Murray
authors.initials: M
authors.lastname: Stewart
mesh_terms: D000595:Amino Acid Sequence; D018360:Crystallography, X-Ray; D026901:Membrane Transport Proteins / Q000737:chemistry / Q000378:metabolism*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000737:chemistry / Q000378:metabolism*; D029543:Nucleocytoplasmic Transport Proteins / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D012331:RNA, Fungal / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000378:metabolism*; D012542:Scattering, Radiation; D017386:Sequence Homology, Amino Acid
chemical_list: C106898:MEX67 protein, S cerevisiae; D026901:Membrane Transport Proteins; C480169:Mtr2 protein, S cerevisiae; D009687:Nuclear Proteins; D029543:Nucleocytoplasmic Transport Proteins; D012331:RNA, Fungal; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D029701:Saccharomyces cerevisiae Proteins