title: Architectural nucleoporins Nup157/170 and Nup133 are structurally related and descend from a second ancestral element.
abstract: The nuclear pore complex (NPC) constitutes one of the largest protein assemblies in the eukaryotic cell and forms the exclusive gateway to the nucleus. The stable, approximately 15-20-MDa scaffold ring of the NPC is built from two multiprotein complexes arranged around a central 8-fold axis. Here we present crystal structures of two large architectural units, yNup170(979-1502) and hNup107(658-925) x hNup133(517-1156), each a constituent of one of the two multiprotein complexes. Conservation of domain arrangement and of tertiary structure suggests that Nup157/170 and Nup133 derived from a common ancestor. Together with the previously established ancestral coatomer element (ACE1), these two elements constitute the major alpha-helical building blocks of the NPC scaffold and define its branched, lattice-like architecture, similar to vesicle coats like COPII. We hypothesize that the extant NPC evolved early during eukaryotic evolution from a rudimentary structure composed of several identical copies of a few ancestral elements, later diversified and specified by gene duplication.
authors.affiliation: Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139.
authors.forename: James R R
authors.initials: JRR
authors.lastname: Whittle
authors.affiliation: Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139. Electronic address: tus@mit.edu.
authors.forename: Thomas U
authors.initials: TU
authors.lastname: Schwartz
mesh_terms: D000595:Amino Acid Sequence; D018360:Crystallography, X-Ray; D019143:Evolution, Molecular; D006801:Humans; D015778:Minor Histocompatibility Antigens; D008958:Models, Molecular; D008969:Molecular Sequence Data; D046912:Multiprotein Complexes / Q000737:chemistry / Q000378:metabolism; D022022:Nuclear Pore / Q000737:chemistry / Q000378:metabolism; D028861:Nuclear Pore Complex Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D017433:Protein Structure, Secondary; D012441:Saccharomyces cerevisiae / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid
chemical_list: D015778:Minor Histocompatibility Antigens; D046912:Multiprotein Complexes; C512772:NUP107 protein, human; C440250:NUP133 protein, human; C097179:NUP157 protein, S cerevisiae; C097178:NUP170 protein, S cerevisiae; C097894:NUP84 protein, S cerevisiae; D028861:Nuclear Pore Complex Proteins; D029701:Saccharomyces cerevisiae Proteins
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