PDBsum entry: 1y8x

Ligase

PDB id: 1y8x

Contents

Protein chains

160 a.a. *

92 a.a. *

Waters ×112

* Residue conservation analysis

PDB id:

1y8x

Name:

Ligase

Title:

Structural basis for recruitment of ubc12 by an e2-binding domain in nedd8's e1

Structure:

Ubiquitin-conjugating enzyme e2 m. Chain: a. Synonym: ubiquitin-protein ligase m, ubiquitin carrier protein m, nedd8-conjugating enzyme ubc12. Engineered: yes. Ubiquitin-activating enzyme e1c. Chain: b. Synonym: nedd8-activating enzyme e1c, ubiquitin-activating enzyme 3 homolog.

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: ube2m, ubc12. Expressed in: escherichia coli. Expression_system_taxid: 562. Gene: ube1c, uba3. Expression_system_taxid: 562

Biol. unit:

Dimer (from PQS)

Resolution:

2.40Å R-factor: 0.242 R-free: 0.259

Authors:

D.T.Huang,A.Paydar,M.Zhuang,M.B.Waddell,J.M.Holton, B.A.Schulman

Key ref:

D.T.Huang et al. (2005). Structural basis for recruitment of Ubc12 by an E2 binding domain in NEDD8's E1. Mol Cell, 17, 341-350. PubMed id: 15694336 DOI: 10.1016/j.molcel.2004.12.020

Date:

13-Dec-04 Release date: 08-Feb-05

Protein chain

P61081  (UBC12_HUMAN) -  NEDD8-conjugating enzyme Ubc12

Seq: 183 a.a.

Struc: 160 a.a.*

Protein chain

Q8TBC4  (UBA3_HUMAN) -  NEDD8-activating enzyme E1 catalytic subunit

Seq: 463 a.a.

Struc: 92 a.a.*

* PDB and UniProt seqs differ at 4 residue positions (black crosses)

 Gene Ontology (GO) functional annotation 

• Biological process: regulation of protein metabolic process (4 terms)
• Biochemical function: acid-amino acid ligase activity (3 terms)

DOI no: 10.1016/j.molcel.2004.12.020

Mol Cell 17:341-350 (2005)

PubMed id: 15694336

Structural basis for recruitment of Ubc12 by an E2 binding domain in NEDD8's E1.

D.T.Huang, A.Paydar, M.Zhuang, M.B.Waddell, J.M.Holton, B.A.Schulman.

ABSTRACT

E2 conjugating enzymes play a central role in ubiquitin and ubiquitin-like protein (ublp) transfer cascades: the E2 accepts the ublp from the E1 enzyme and then the E2 often interacts with an E3 enzyme to promote ublp transfer to the target. We report here the crystal structure of a complex between the C-terminal domain from NEDD8's heterodimeric E1 (APPBP1-UBA3) and the catalytic core domain of NEDD8's E2 (Ubc12). The structure and associated mutational analyses reveal molecular details of Ubc12 recruitment by NEDD8's E1. Interestingly, the E1's Ubc12 binding domain resembles ubiquitin and recruits Ubc12 in a manner mimicking ubiquitin's interactions with ubiquitin binding domains. Structural comparison with E2-E3 complexes indicates that the E1 and E3 binding sites on Ubc12 may overlap and raises the possibility that crosstalk between E1 and E3 interacting with an E2 could influence the specificity and processivity of ublp transfer.

Selected figure(s)

Figure 5.
Figure 5. Recognition of Common E2 Structural Elements by NE1^ufd and E3sStructures of NE1^ufd in complex with the E2 Ubc12^core, the E3 c-Cbl in complex with the E2 UbcH7 (Zheng et al., 2000), and the RING domain of the E3 CNOT4 in complex with the E2 UbcH5B (Dominguez et al., 2004), shown from left to right, with UbcH7 and UbcH5B in the same orientation as Ubc12^core. The E2 binding domain of the E1, NE1^ufd, is shown in red, and of the E3s, c-Cbl and CNOT4, are shown in magenta. The E2s Ubc12^core, UbcH7, and UbcH5B are shown in cyan. The corresponding regions of the first turn of the N-terminal helix in Ubc12^core, UbcH7, and UbcH5B are labeled “α1,” and are involved in binding to NE1^ufd, c-Cbl, and CNOT4, respectively.

Figure 6.
Figure 6. NE1^ufd Recruits Ubc12^core in a Manner Resembling Ubiquitin Interactions with Ubiquitin Binding DomainsStructures of NE1^ufd-Ubc12^core, ubiquitin in complex with the CUE domain from yeast Cue2 (Kang et al., 2003), ubiquitin in complex with the NZF domain of Npl4 (Alam et al., 2004), ubiquitin in complex with the UEV domain of TSG101 (Sundquist et al., 2004), and ubiquitin in complex with the UIM domain of Vps27 (Swanson et al., 2003) are shown from left to right, with ubiquitin in the same orientation as NE1^ufd. NE1^ufd and ubiquitin are shown in red, Ubc12^core and the ubiquitin binding domains are shown in cyan.

The above figures are reprinted by permission from Cell Press: Mol Cell (2005, 17, 341-350) copyright 2005.

Figures were selected by the author.