Structure of a trimeric nucleoporin complex reveals alternate oligomerization states

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 106; no. 42; pp. 17693 - 17698
• Main Authors: Nagy, Vivien, Hsia, Kuo-Chiang, Debler, Erik W, Kampmann, Martin, Davenport, Andrew M, Blobel, Günter, Hoelz, André
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 20.10.2009; National Acad Sciences
• Subjects: Architecture; Binding Sites; Binding, Competitive; Biochemistry; Biological Sciences; Cells; CRYSTAL STRUCTURE; Crystallography, X-Ray; ELECTRON MICROSCOPY; MATERIALS SCIENCE; Microscopy; Models, Molecular; Multiprotein Complexes - chemistry; Nuclear membrane; Nuclear pore; Nuclear Pore - chemistry; Nuclear pore complex proteins; Nuclear Pore Complex Proteins - chemistry; Promiscuity; Protein Interaction Domains and Motifs; Protein Structure, Quaternary; Proteins; RESOLUTION; Saccharomyces cerevisiae - chemistry; Saccharomyces cerevisiae Proteins - chemistry; SOLENOIDS; Yeasts
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.0909373106

The heptameric Nup84 complex constitutes an evolutionarily conserved building block of the nuclear pore complex. Here, we present the crystal structure of the heterotrimeric Sec13·Nup145C·Nup84 complex, the centerpiece of the heptamer, at 3.2-Å resolution. Nup84 forms a U-shaped α-helical solenoid domain, topologically similar to two other members of the heptamer, Nup145C and Nup85. The interaction between Nup84 and Nup145C is mediated via a hydrophobic interface located in the kink regions of the two solenoids that is reinforced by additional interactions of two long Nup84 loops. The Nup84 binding site partially overlaps with the homo-dimerization interface of Nup145C, suggesting competing binding events. Fitting of the elongated Z-shaped heterotrimer into electron microscopy (EM) envelopes of the heptamer indicates that structural changes occur at the Nup145C·Nup84 interface. Docking the crystal structures of all heptamer components into the EM envelope constitutes a major advance toward the completion of the structural characterization of the Nup84 complex.