3NTW
Structure of the MLLE domain of EDD in complex with a PAM2 peptide from Paip1
Summary for 3NTW
| Entry DOI | 10.2210/pdb3ntw/pdb |
| Descriptor | E3 ubiquitin-protein ligase UBR5, Polyadenylate-binding protein-interacting protein 1 (3 entities in total) |
| Functional Keywords | protein-protein complex, mlle domain, pabc domain, protein binding |
| Biological source | Rattus norvegicus (Rat) More |
| Total number of polymer chains | 4 |
| Total formula weight | 19062.00 |
| Authors | Kozlov, G.,Gehring, K. (deposition date: 2010-07-05, release date: 2011-07-06, Last modification date: 2023-09-06) |
| Primary citation | Munoz-Escobar, J.,Matta-Camacho, E.,Kozlov, G.,Gehring, K. The MLLE domain of the ubiquitin ligase UBR5 binds to its catalytic domain to regulate substrate binding. J. Biol. Chem., 290:22841-22850, 2015 Cited by PubMed Abstract: E3 ubiquitin ligases catalyze the transfer of ubiquitin from an E2-conjugating enzyme to a substrate. UBR5, homologous to the E6AP C terminus (HECT)-type E3 ligase, mediates the ubiquitination of proteins involved in translation regulation, DNA damage response, and gluconeogenesis. In addition, UBR5 functions in a ligase-independent manner by prompting protein/protein interactions without ubiquitination of the binding partner. Despite recent functional studies, the mechanisms involved in substrate recognition and selective ubiquitination of its binding partners remain elusive. The C terminus of UBR5 harbors the HECT catalytic domain and an adjacent MLLE domain. MLLE domains mediate protein/protein interactions through the binding of a conserved peptide motif, termed PAM2. Here, we characterize the binding properties of the UBR5 MLLE domain to PAM2 peptides from Paip1 and GW182. The crystal structure with a Paip1 PAM2 peptide reveals the network of hydrophobic and ionic interactions that drive binding. In addition, we identify a novel interaction of the MLLE domain with the adjacent HECT domain mediated by a PAM2-like sequence. Our results confirm the role of the MLLE domain of UBR5 in substrate recruitment and suggest a potential role in regulating UBR5 ligase activity. PubMed: 26224628DOI: 10.1074/jbc.M115.672246 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.6 Å) |
Structure validation
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