PDBsum entry 4xib

Ligase

PDB id: 4xib

Contents

Protein chain

362 a.a.

Ligands

ASN-ILE-ILE-LYS-ASN-THR-TRP

SO4 ×2

Metals

_ZN ×2

Waters ×108

PDB id:

4xib

Name:

Ligase

Title:

Crystal structure of the mzm-rep domains of mind bomb 1 in complex with fly delta n-box peptide

Structure:

E3 ubiquitin-protein ligase mib1. Chain: a. Synonym: dapk-interacting protein 1,dip-1,mind bomb homolog 1,zinc finger zz type with ankyrin repeat domain protein 2. Engineered: yes. Delta n-box peptide. Chain: c. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: mib1, dip1, kiaa1323, zzank2. Expressed in: escherichia coli. Expression_system_taxid: 562. Synthetic: yes. Drosophila melanogaster. Organism_taxid: 7227

Resolution:

2.15Å R-factor: 0.212 R-free: 0.244

Authors:

B.J.Mcmillan,S.C.Blacklow

Key ref:

B.J.McMillan et al. (2015). A tail of two sites: a bipartite mechanism for recognition of notch ligands by mind bomb E3 ligases. Mol Cell, 57, 912-924. PubMed id: 25747658 DOI: 10.1016/j.molcel.2015.01.019

Date:

06-Jan-15 Release date: 18-Mar-15

Protein chain

Q86YT6  (MIB1_HUMAN) -  E3 ubiquitin-protein ligase MIB1 from Homo sapiens

Seq: 1006 a.a.

Struc: 362 a.a.*

* PDB and UniProt seqs differ at 1 residue position (black cross)

Enzyme reactions

• Enzyme class: E.C.2.3.2.27 - RING-type E3 ubiquitin transferase.
• Reaction: S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine + [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-cysteine + N₆- ubiquitinyl-[acceptor protein]-L-lysine

DOI no: 10.1016/j.molcel.2015.01.019

Mol Cell 57:912-924 (2015)

PubMed id: 25747658

A tail of two sites: a bipartite mechanism for recognition of notch ligands by mind bomb E3 ligases.

B.J.McMillan, B.Schnute, N.Ohlenhard, B.Zimmerman, L.Miles, N.Beglova, T.Klein, S.C.Blacklow.

ABSTRACT

Mind bomb (Mib) proteins are large, multi-domain E3 ligases that promote ubiquitination of the cytoplasmic tails of Notch ligands. This ubiquitination step marks the ligand proteins for epsin-dependent endocytosis, which is critical for in vivo Notch receptor activation. We present here crystal structures of the substrate recognition domains of Mib1, both in isolation and in complex with peptides derived from Notch ligands. The structures, in combination with biochemical, cellular, and in vivo assays, show that Mib1 contains two independent substrate recognition domains that engage two distinct epitopes from the cytoplasmic tail of the ligand Jagged1, one in the intracellular membrane proximal region and the other near the C terminus. Together, these studies provide insights into the mechanism of ubiquitin transfer by Mind bomb E3 ligases, illuminate a key event in ligand-induced activation of Notch receptors, and identify a potential target for therapeutic modulation of Notch signal transduction in disease.