3NTW

Structure of the MLLE domain of EDD in complex with a PAM2 peptide from Paip1

3NTW の概要

• エントリーDOI: 10.2210/pdb3ntw/pdb
• 分子名称: E3 ubiquitin-protein ligase UBR5, Polyadenylate-binding protein-interacting protein 1 (3 entities in total)
• 機能のキーワード: protein-protein complex, mlle domain, pabc domain, protein binding
• 由来する生物種: Rattus norvegicus (Rat); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 19062.00

構造登録者

Kozlov, G.,Gehring, K. (登録日: 2010-07-05, 公開日: 2011-07-06, 最終更新日: 2023-09-06)

主引用文献

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

実験手法

X-RAY DIFFRACTION (2.6 Å)