Structural evidence for common ancestry of the nuclear pore complex and vesicle coats.
Nuclear pore complexes (NPCs) facilitate nucleocytoplasmic transport. These massive assemblies comprise an eightfold symmetric scaffold of architectural proteins and central-channel phenylalanine-glycine-repeat proteins forming the transport barrier. We determined the nucleoporin 85 (Nup85)*Seh1 structure, a module in the heptameric Nup84 complex, at 3.5 angstroms resolution. Structural, biochemical, and genetic analyses position the Nup84 complex in two peripheral NPC rings. We establish a conserved tripartite element, the ancestral coatomer element ACE1, that reoccurs in several nucleoporins and vesicle coat proteins, providing structural evidence of coevolution from a common ancestor. We identified interactions that define the organization of the Nup84 complex on the basis of comparison with vesicle coats and confirmed the sites by mutagenesis. We propose that the NPC scaffold, like vesicle coats, is composed of polygons with vertices and edges forming a membrane-proximal lattice that provides docking sites for additional nucleoporins.
Brohawn
Stephen G
SG
Department of Biology, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA.
Leksa
Nina C
NC
Spear
Eric D
ED
Rajashankar
Kanagalaghatta R
KR
Schwartz
Thomas U
TU
D000595:Amino Acid Sequence; D001665:Binding Sites; D018699:Coated Vesicles / Q000737:chemistry*; D018360:Crystallography, X-Ray; D019281:Dimerization; D019143:Evolution, Molecular; D008565:Membrane Proteins / Q000737:chemistry / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016296:Mutagenesis; D022022:Nuclear Pore / Q000737:chemistry*; D028861:Nuclear Pore Complex Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D009687:Nuclear Proteins / Q000737:chemistry / Q000378:metabolism; D011487:Protein Conformation; D017510:Protein Folding; D017433:Protein Structure, Secondary; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D033921:Vesicular Transport Proteins / Q000737:chemistry*
D008565:Membrane Proteins; C082533:NIC96 protein, S cerevisiae; C088627:NUP145 protein, S cerevisiae; C097894:NUP84 protein, S cerevisiae; C106899:NUP85 protein, S cerevisiae; D028861:Nuclear Pore Complex Proteins; D009687:Nuclear Proteins; C079620:SEC13 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; C533526:Seh1 protein, S cerevisiae; D033921:Vesicular Transport Proteins