PDBsum entry 2oit

Oncoprotein

PDB id: 2oit

Contents

Protein chain

434 a.a. *

Ligands

MES

Waters ×465

* Residue conservation analysis

PDB id:

2oit

Name:

Oncoprotein

Title:

Crystal structure of the n-terminal domain of the human proto-oncogene nup214/can

Structure:

Nucleoporin 214kda. Chain: a. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: nup214. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.

Resolution:

1.65Å R-factor: 0.199 R-free: 0.237

Authors:

J.Napetschnig,G.Blobel,A.Hoelz

Key ref:

J.Napetschnig et al. (2007). Crystal structure of the N-terminal domain of the human protooncogene Nup214/CAN. Proc Natl Acad Sci U S A, 104, 1783-1788. PubMed id: 17264208 DOI: 10.1073/pnas.0610828104

Date:

11-Jan-07 Release date: 06-Feb-07

Protein chain

P35658  (NU214_HUMAN) -  Nuclear pore complex protein Nup214 from Homo sapiens

Seq: 2090 a.a.

Struc: 434 a.a.

DOI no: 10.1073/pnas.0610828104

Proc Natl Acad Sci U S A 104:1783-1788 (2007)

PubMed id: 17264208

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

J.Napetschnig, G.Blobel, A.Hoelz.

ABSTRACT

The mammalian nuclear pore complex (NPC) is an approximately 120-MDa proteinaceous assembly consisting of approximately 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-A resolution. The structure reveals a seven-bladed beta-propeller followed by a 30-residue C-terminal extended peptide segment, which folds back onto the beta-propeller and binds to its bottom face. The beta-propeller repeats lack any recognizable sequence motif and are distinguished by extensive insertions between the canonical beta-strands. We propose a mechanism by which the C-terminal peptide extension is involved in NPC assembly.

Selected figure(s)

Figure 1.
Fig. 1. The structure of the NTD of human Nup214. (A) Domain structure of Nup214 and Nup159. The construct used for crystallization is boxed red, and two phosphorylation sites of the NTD are indicated. Residues observed in the crystal structures are boxed in blue. (B) Schematic representation of the NTD structure. The blades of the -propeller are labeled from 1 to 7. The CTE is shown in blue, and -strands forming the double-Velcro closure are indicated with an asterisk. (C) Ribbon representation of the NTD structure. A 180°-rotated view is shown on the right. As a reference, the strands of blade 3 are labeled A–D. The blades of the -propeller and the CTE are labeled as in B. The helical insertions are shown in pink. (D) Ribbon representation of side views of the structure of the NTD. The view on the right is rotated by 180°.

Figure 3.
Fig. 3. CTE binding to the bottom face of the -propeller. (A) The surface of the Nup214 -propeller is colored according to the electrostatic potential from –10 k[B]T (red) to + 10 k[B]T (blue). The CTE is shown in blue coil representation with the side chains in ball-and-stick representation. The black box indicates the region magnified in D. (B) Hydrophobic interactions of CTE residues Val-410, Leu-413, and Leu-414 (yellow). (C) Interactions of Leu-420 and Leu-422 (yellow) with residues of the -propeller. Hydrophobic pocket-forming residues are shown in gray. The surface of the -propeller is colored as in A. (D) Schematic representation of the contacts between the -propeller and the CTE. Hydrogen and ionic bonds are indicated by orange dashed lines and van der Waals contacts with gray grooves.

Figures were selected by the author.