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

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: 26224628
DOI: 10.1074/jbc.M115.672246

Experimental method

X-RAY DIFFRACTION (2.6 Å)