1TT5

Structure of APPBP1-UBA3-Ubc12N26: a unique E1-E2 interaction required for optimal conjugation of the ubiquitin-like protein NEDD8

Summary for 1TT5

• Entry DOI: 10.2210/pdb1tt5/pdb
• Descriptor: amyloid protein-binding protein 1, ubiquitin-activating enzyme E1C isoform 1, Ubiquitin-conjugating enzyme E2 M, ... (5 entities in total)
• Functional Keywords: cell cycle, ligase
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 6
• Total formula weight: 223428.73

Authors

Huang, D.T.,Miller, D.W.,Mathew, R.,Cassell, R.,Holton, J.M.,Roussel, M.F.,Schulman, B.A. (deposition date: 2004-06-21, release date: 2004-09-14, Last modification date: 2024-02-14)

Primary citation

Huang, D.T.,Miller, D.W.,Mathew, R.,Cassell, R.,Holton, J.M.,Roussel, M.F.,Schulman, B.A.
A unique E1-E2 interaction required for optimal conjugation of the ubiquitin-like protein NEDD8.
Nat.Struct.Mol.Biol., 11:927-935, 2004

PubMed Abstract: Ubiquitin-like proteins (UBLs) such as NEDD8 are transferred to their targets by distinct, parallel, multienzyme cascades that involve the sequential action of E1, E2 and E3 enzymes. How do enzymes within a particular UBL conjugation cascade interact with each other? We report here that the unique N-terminal sequence of NEDD8's E2, Ubc12, selectively recruits NEDD8's E1 to promote thioester formation between Ubc12 and NEDD8. A peptide corresponding to Ubc12's N terminus (Ubc12N26) specifically binds and inhibits NEDD8's E1, the heterodimeric APPBP1-UBA3 complex. The structure of APPBP1-UBA3- Ubc12N26 reveals conserved Ubc12 residues docking in a groove generated by loops conserved in UBA3s but not other E1s. These data explain why the Ubc12-UBA3 interaction is unique to the NEDD8 pathway. These studies define a novel mechanism for E1-E2 interaction and show how enzymes within a particular UBL conjugation cascade can be tethered together by unique protein-protein interactions emanating from their common structural scaffolds.

PubMed: 15361859
DOI: 10.1038/nsmb826

Experimental method

X-RAY DIFFRACTION (2.6 Å)