PDBsum entry: 1jn5

Transport protein

PDB id: 1jn5

Contents

Protein chains

136 a.a. *

182 a.a. *

Ligands

PRO-GLY-PHE-GLY-GLN-GLY

* Residue conservation analysis

PDB id:

1jn5

Name:

Transport protein

Title:

Structural basis for the recognition of a nucleoporin fg- repeat by the ntf2-like domain of tap-p15 mRNA export factor

Structure:

P15. Chain: a. Synonym: ntf2-related export protein 1. Engineered: yes. Tap. Chain: b. Fragment: residues 371-619. Synonym: tip associating protein. Engineered: yes.

Source:

Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008. Synthetic: yes. Other_details: this sequence occurs naturally in humans.

Biol. unit:

Trimer (from PQS)

Resolution:

2.80Å R-factor: 0.241 R-free: 0.267

Authors:

S.Fribourg,I.C.Braun,E.Izaurralde,E.Conti

Key ref:

S.Fribourg et al. (2001). Structural basis for the recognition of a nucleoporin FG repeat by the NTF2-like domain of the TAP/p15 mRNA nuclear export factor. Mol Cell, 8, 645-656. PubMed id: 11583626 DOI: 10.1016/S1097-2765(01)00348-3

Date:

23-Jul-01 Release date: 17-Oct-01

Protein chain

Q9UKK6  (NXT1_HUMAN) -  NTF2-related export protein 1

Seq: 140 a.a.

Struc: 136 a.a.

Protein chain

Q9UBU9  (NXF1_HUMAN) -  Nuclear RNA export factor 1

Seq: 619 a.a.

Struc: 182 a.a.*

* PDB and UniProt seqs differ at 1 residue position (black cross)

 Gene Ontology (GO) functional annotation 

• Cellular component: intracellular (4 terms)
• Biological process: transport (5 terms)
• Biochemical function: protein binding (2 terms)

DOI no: 10.1016/S1097-2765(01)00348-3

Mol Cell 8:645-656 (2001)

PubMed id: 11583626

Structural basis for the recognition of a nucleoporin FG repeat by the NTF2-like domain of the TAP/p15 mRNA nuclear export factor.

S.Fribourg, I.C.Braun, E.Izaurralde, E.Conti.

ABSTRACT

TAP-p15 heterodimers have been implicated in the export of mRNAs through nuclear pore complexes (NPCs). We report a structural analysis of the interaction domains of TAP and p15 in a ternary complex with a Phe-Gly (FG) repeat of an NPC component. The TAP-p15 heterodimer is structurally similar to the homodimeric transport factor NTF2, but unlike NTF2, it is incompatible with either homodimerization or Ran binding. The NTF2-like heterodimer functions as a single structural unit in recognizing an FG repeat at a hydrophobic pocket present only on TAP and not on p15. This FG binding site interacts synergistically with a second site at the C terminus of TAP to mediate mRNA transport through the pore. In general, our findings suggest that FG repeats bind with a similar conformation to different classes of transport factors.

Selected figure(s)

Figure 3.
Figure 3. FG Nucleoporin Recognition by Transport Factors(A) Recognition of nucleoporin FG repeats by nucleocytoplasmic transport factors. Structure of an FG-containing peptide (in black) bound to the NTF2-like domain of TAP. The 2.8 Å resolution electron density from a simulated annealing omit map was computed after removal of the peptide from the refined model and contoured at 3σ. The phenylalanine of the peptide inserts its side chain into a pocket formed by a set of residues shown in red.(B) Surface representation showing the hydrophobic FG binding pocket of TAP with the bound nucleoporin repeat peptide. The surface is colored according to the electrostatic potential and viewed in an orientation similar to (A). This figure and similar ones were generated with the program GRASP, with negatively charged areas shown in red and positively charged in blue (Nicholls et al., 1991).(C) The corresponding surface of p15 is more hydrophilic and presents no accessible pocket for FG-containing nucleoporins.(D) NTF2 has a hydrophobic cavity at the equivalent structural position to the FG binding pocket of the NTF2-like domain of TAP in (A). Among the hydrophobic residues that line the pocket (green), Trp7 has previously been shown by mutagenesis experiments to be important for FG nucleoporin binding (Bayliss et al., 1999).(E) Recognition of an FxFG-containing peptide on the importin β surface (Bayliss et al., 2000). One phenylalanine residue in particular is inserted into a pocket lined by the residues indicated.(F) Superposition of the x-Phe-Gly residues of nucleoporin repeats bound to TAP NTF2-like domain (black) and to importin β (gray; Bayliss et al., 2000) shows they have a similar conformation when bound to the two different transport factors. The lighter gray corresponds to the FG motif bound at the principal nucleoporin binding site of importin β, and corresponds to the structure shown in (E)

Figure 5.
Figure 5. RanGDP Binding Abilities of NTF2-like Domains(A) Structure of an NTF2 monomer (green) bound to RanGDP (blue; Stewart et al., 1998). In particular, the Phe72 residue from the switch II region of RanGDP (see enlargement) interacts with a pocket of NTF2 lined by hydrophobic residues (green; Stewart et al., 1998).(B) The structure of the NTF2-like domain of TAP is incompatible with a similar RanGDP binding due to the presence of the insertion loop.(C) The structure of p15 shows that certain residues are similarly positioned in the RanGDP binding pocket of NTF2 (see Trp47 and Phe101). However, the access of RanGDP is prevented by the occluding residues Phe135 and Arg107

The above figures are reprinted by permission from Cell Press: Mol Cell (2001, 8, 645-656) copyright 2001.

Figures were selected by the author.