PDBsum entry 1ndd

Signaling protein

PDB id: 1ndd

Contents

Protein chains

74 a.a. *

Ligands

SO4 ×4

Metals

_CL ×2

Waters ×193

* Residue conservation analysis

PDB id:

1ndd

Name:

Signaling protein

Title:

Structure of nedd8

Structure:

Protein (ubiquitin-like protein nedd8). Chain: a, b, c, d. Synonym: nedd8. Engineered: yes. Other_details: human nedd8 ubiquitin-like protein monomer with 4 molecules in the crystallographic asymmetric unit

Source:

Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562. Other_details: expressed in e.Coli

Biol. unit:

Tetramer (from PQS)

Resolution:

1.60Å R-factor: 0.219 R-free: 0.300

Authors:

F.G.Whitby,G.Xia,C.M.Pickart,C.P.Hill

Key ref:

F.G.Whitby et al. (1998). Crystal structure of the human ubiquitin-like protein NEDD8 and interactions with ubiquitin pathway enzymes. J Biol Chem, 273, 34983-34991. PubMed id: 9857030 DOI: 10.1074/jbc.273.52.34983

Date:

21-Aug-98 Release date: 23-Feb-99

Protein chains

Q15843  (NEDD8_HUMAN) -  NEDD8 from Homo sapiens

Seq: 81 a.a.

Struc: 74 a.a.

DOI no: 10.1074/jbc.273.52.34983

J Biol Chem 273:34983-34991 (1998)

PubMed id: 9857030

Crystal structure of the human ubiquitin-like protein NEDD8 and interactions with ubiquitin pathway enzymes.

F.G.Whitby, G.Xia, C.M.Pickart, C.P.Hill.

ABSTRACT

The NEDD8/Rub1 class of ubiquitin-like proteins has been implicated in progression of the cell cycle from G1 into S phase. These molecules undergo a metabolism that parallels that of ubiquitin and involves specific interactions with many different proteins. We report here the crystal structure of recombinant human NEDD8 refined at 1.6-A resolution to an R factor of 21.9%. As expected from the high sequence similarity (57% identical), the NEDD8 structure closely resembles that reported previously for ubiquitin. We also show that recombinant human NEDD8 protein is activated, albeit inefficiently, by the ubiquitin-activating (E1) enzyme and that NEDD8 can be transferred from E1 to the ubiquitin conjugating enzyme E2-25K. E2-25K adds NEDD8 to a polyubiquitin chain with an efficiency similar to that of ubiquitin. A chimeric tetramer composed of three ubiquitins and one histidine-tagged NEDD8 binds to the 26 S proteasome with an affinity similar to that of tetraubiquitin. Seven residues that differ from the corresponding residues in ubiquitin, but are conserved between NEDD8 orthologs, are candidates for mediating interactions with NEDD8-specific partners. One such residue, Ala-72 (Arg in ubiquitin), is shown to perform a key role in selecting against reaction with the ubiquitin E1 enzyme, thereby acting to prevent the inappropriate diversion of NEDD8 into ubiquitin-specific pathways.

Selected figure(s)

Figure 3.
Fig. 3. Stereoview ribbon representation of NEDD8. N and C termini are labeled N and C. Secondary structure was defined with PROMOTIF (59). Helices are colored green: helix 1, residues 23-34; helix 2, 38-40; helix 3, 56-59. Helix 1 is type , whereas helices 2 and 3 are type 3[10]. According to the strict definitions used by PROMOTIF, helix 2 does not occur in two of the four NEDD8 molecules in the asymmetric unit, although the conformations are close to those of standard helices. strands are colored red: strand 1, residues 2-6; strand 2, 12-16; strand 3, 41-45, strand 4, 48-49; strand 5, 66-71. Strand 1 has one extra residue in one of the four molecules in the asymmetric unit. Residues discussed in the text are shown explicitly.

Figure 6.
Fig. 6. Space-filling representation of conserved and divergent residues. Three views of NEDD8 are shown. The front view is related to the orientation of Fig. 3 by a rotation about the vertical axis of approximately 90° and a twist of approximately 20°. Notice that the residues Glu-31, Glu-28, and Arg-25, are labeled at the side of the front view and are in the center of Fig. 3. The color code is the same as the text background colors of Fig. 4; invariant residues are magenta, conserved/divergent residues are yellow, and divergent residues are blue. The C terminus is labeled with a C.

The above figures are reprinted by permission from the ASBMB: J Biol Chem (1998, 273, 34983-34991) copyright 1998.

Figures were selected by an automated process.