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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Amino Acid Sequence
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Crystallography, X-Ray
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Evolution, Molecular*
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Humans
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Minor Histocompatibility Antigens
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Models, Molecular
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Molecular Sequence Data
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Multiprotein Complexes / chemistry
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Multiprotein Complexes / metabolism
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Nuclear Pore / chemistry
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Nuclear Pore / metabolism
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Nuclear Pore Complex Proteins / chemistry*
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Nuclear Pore Complex Proteins / genetics
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Nuclear Pore Complex Proteins / metabolism
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Protein Structure, Secondary
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Saccharomyces cerevisiae / metabolism
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Saccharomyces cerevisiae Proteins / chemistry*
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Saccharomyces cerevisiae Proteins / genetics
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Saccharomyces cerevisiae Proteins / metabolism
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Sequence Alignment
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Sequence Homology, Amino Acid
Substances
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Minor Histocompatibility Antigens
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Multiprotein Complexes
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NUP107 protein, human
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NUP133 protein, human
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NUP157 protein, S cerevisiae
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NUP170 protein, S cerevisiae
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NUP84 protein, S cerevisiae
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Nuclear Pore Complex Proteins
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Saccharomyces cerevisiae Proteins
Associated data
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PDB/3I4R
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PDB/3I5P
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PDB/3I5Q