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Published February 6, 2007 | Published + Supplemental Material
Journal Article Open

Crystal structure of the N-terminal domain of the human protooncogene Nup214/CAN


The mammalian nuclear pore complex (NPC) is an ≈120-MDa proteinaceous assembly consisting of ≈30 proteins and is the sole gate in the nuclear envelope. The human protooncogene Nup214 was first identified as a target for chromosomal translocation involved in leukemogenesis. Nup214 is located on the cytoplasmic face of the NPC and is implicated in anchoring the cytoplasmic filaments of the NPC and recruiting the RNA helicase Ddx19. Here, we present the crystal structure of the human Nup214 N-terminal domain at 1.65-Å resolution. The structure reveals a seven-bladed β-propeller followed by a 30-residue C-terminal extended peptide segment, which folds back onto the β-propeller and binds to its bottom face. The β-propeller repeats lack any recognizable sequence motif and are distinguished by extensive insertions between the canonical β-strands. We propose a mechanism by which the C-terminal peptide extension is involved in NPC assembly.

Additional Information

© 2007 National Academy of Sciences. Contributed by Günter Blobel, December 6, 2006 (received for review November 22, 2006). We dedicate this paper to Henning Friedrich. We thank the Kazusa DNA Research Institute for reagents, B. Manjasetty (National Synchrotron Light Source) and C. Ralston (Advanced Light Source) for excellent scientific support and help with x-ray measurements; J. Janz for help with ITC measurements; S. Etherton and S. Lawrie for help with editing the manuscript; and K. Hsia, M. Kampmann, I. Melcak, V. Nagy, A. Patke, and P. Stavropoulos for comments on the manuscript. Peptide synthesis was performed by The Rockefeller University Protein Center. This work was supported by a Predoctoral Fellowship from the Women in Science Foundation (to J.N.) and a Grant from the Leukemia and Lymphoma Society (to A.H.). G.B. is an Investigator of the Howard Hughes Medical Institute. Author contributions: J.N. and A.H. designed research; J.N. and A.H. performed research; J.N., G.B., and A.H. analyzed data; and J.N. and A.H. wrote the paper. The authors declare no conflict of interest. Data deposition: The structure factors and atomic coordinates have been deposited in the Protein Data Bank, www.pdb.org (PDB ID code 2OIT). This article contains supporting information online at www.pnas.org/cgi/content/full/0610828104/DC1.

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Supplemental Material - 10828Fig10.jpg

Supplemental Material - 10828Fig6.jpg

Supplemental Material - 10828Fig7.jpg

Supplemental Material - 10828Fig8.jpg

Supplemental Material - 10828Fig9.jpg


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August 22, 2023
October 20, 2023