title: Structural evolution of the membrane-coating module of the nuclear pore complex.
abstract: The coatomer module of the nuclear pore complex borders the cylinder-like nuclear pore-membrane domain of the nuclear envelope. In evolution, a single coatomer module increases in size from hetero-heptamer (Saccharomyces cerevisiae) to hetero-octamer (Schizosaccharomyces pombe) to hetero-nonamer (Metazoa). Notably, the heptamer-octamer transition proceeds through the acquisition of the nucleoporin Nup37. How Nup37 contacts the heptamer remained unknown. Using recombinant nucleoporins, we show that Sp-Nup37 specifically binds the Sp-Nup120 member of the hetero-heptamer but does not bind an Sc-Nup120 homolog. To elucidate the Nup37-Nup120 interaction at the atomic level, we carried out crystallographic analyses of Sp-Nup37 alone and in a complex with an N-terminal, ~110-kDa fragment of Sp-Nup120 comprising residues 1-950. Corroborating structural predictions, we determined that Nup37 folds into a seven-bladed β-propeller. Several disordered surface regions of the Nup37 β-propeller assume structure when bound to Sp-Nup120. The N-terminal domain of Sp-Nup120(1-950) also folds into a seven-bladed propeller with a markedly protruding 6D-7A insert and is followed by a contorted helical domain. Conspicuously, this 6D-7A insert contains an extension of 50 residues which also is highly conserved in Metazoa but is absent in Sc-Nup120. Strikingly, numerous contacts with the Nup37 β-propeller are located on this extension of the 6D-7A insert. Another contact region is situated toward the end of the helical region of Sp-Nup120(1-950). Our findings provide information about the evolution and the assembly of the coatomer module of the nuclear pore complex.
authors.affiliation: Laboratory of Cell Biology, Rockefeller University, New York, NY 10065, USA.
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Liu
authors.forename: Jana M
authors.initials: JM
authors.lastname: Mitchell
authors.forename: Richard W
authors.initials: RW
authors.lastname: Wozniak
authors.forename: Günter
authors.initials: G
authors.lastname: Blobel
authors.forename: Jie
authors.initials: J
authors.lastname: Fan
mesh_terms: D000595:Amino Acid Sequence; D005075:Biological Evolution; D018360:Crystallography, X-Ray; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009685:Nuclear Envelope / Q000737:chemistry* / Q000378:metabolism; D022022:Nuclear Pore / Q000737:chemistry* / Q000378:metabolism; D028861:Nuclear Pore Complex Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding; D017510:Protein Folding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D012568:Schizosaccharomyces / Q000235:genetics / Q000378:metabolism; D029702:Schizosaccharomyces pombe Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D017386:Sequence Homology, Amino Acid
chemical_list: C097740:NUP120 protein, S cerevisiae; C577138:NUP37 protein, S pombe; D028861:Nuclear Pore Complex Proteins; C576664:Nup120 protein, S pombe; D029701:Saccharomyces cerevisiae Proteins; D029702:Schizosaccharomyces pombe Proteins