PDBsum entry 6vee

Peptide binding protein

PDB id: 6vee

Contents

Protein chain

184 a.a.

PDB id:

6vee

Name:

Peptide binding protein

Title:

Solution structure of the ttd and linker region of mouse uhrf1 (np95)

Structure:

E3 ubiquitin-protein ligase uhrf1. Chain: a. Synonym: nuclear protein 95,nuclear zinc finger protein np95,ring- type e3 ubiquitin transferase uhrf1,ubiquitin-like phd and ring finger domain-containing protein 1,muhrf1,ubiquitin-like-containing phd and ring finger domains protein 1. Engineered: yes

Source:

Mus musculus. Mouse. Organism_taxid: 10090. Gene: uhrf1, np95. Expressed in: escherichia coli. Expression_system_taxid: 562

NMR struc:

20 models

Authors:

A.Lemak,S.Houliston,S.Duan,C.H.Arrowsmith

Key ref:

M.Tauber et al. (2020). Alternative splicing and allosteric regulation modulate the chromatin binding of UHRF1. Nucleic Acids Res, 48, 7728-7747. PubMed id: 32609811 DOI: 10.1093/nar/gkaa520

Date:

31-Dec-19 Release date: 17-Jun-20

Protein chain

Q8VDF2  (UHRF1_MOUSE) -  E3 ubiquitin-protein ligase UHRF1 from Mus musculus

Seq: 782 a.a.

Struc: 184 a.a.

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: 10.1093/nar/gkaa520

Nucleic Acids Res 48:7728-7747 (2020)

PubMed id: 32609811

Alternative splicing and allosteric regulation modulate the chromatin binding of UHRF1.

M.Tauber, S.Kreuz, A.Lemak, P.Mandal, Z.Yerkesh, A.Veluchamy, B.Al-Gashgari, A.Aljahani, L.V.Cortés-Medina, D.Azhibek, L.Fan, M.S.Ong, S.Duan, S.Houliston, C.H.Arrowsmith, W.Fischle.

ABSTRACT

UHRF1 is an important epigenetic regulator associated with apoptosis and tumour development. It is a multidomain protein that integrates readout of different histone modification states and DNA methylation with enzymatic histone ubiquitylation activity. Emerging evidence indicates that the chromatin-binding and enzymatic modules of UHRF1 do not act in isolation but interplay in a coordinated and regulated manner. Here, we compared two splicing variants (V1, V2) of murine UHRF1 (mUHRF1) with human UHRF1 (hUHRF1). We show that insertion of nine amino acids in a linker region connecting the different TTD and PHD histone modification-binding domains causes distinct H3K9me3-binding behaviour of mUHRF1 V1. Structural analysis suggests that in mUHRF1 V1, in contrast to V2 and hUHRF1, the linker is anchored in a surface groove of the TTD domain, resulting in creation of a coupled TTD-PHD module. This establishes multivalent, synergistic H3-tail binding causing distinct cellular localization and enhanced H3K9me3-nucleosome ubiquitylation activity. In contrast to hUHRF1, H3K9me3-binding of the murine proteins is not allosterically regulated by phosphatidylinositol 5-phosphate that interacts with a separate less-conserved polybasic linker region of the protein. Our results highlight the importance of flexible linkers in regulating multidomain chromatin binding proteins and point to divergent evolution of their regulation.