PDBsum entry 3vuy

Protein binding/metal binding protein

PDB id: 3vuy

Contents

Protein chains

76 a.a.

33 a.a.

31 a.a.

32 a.a.

Metals

__K ×3

_ZN ×3

Waters ×184

PDB id:

3vuy

Name:

Protein binding/metal binding protein

Title:

Crystal structure of a20 zf7 in complex with linear tetraubiquitin

Structure:

Polyubiquitin-c. Chain: a, c, b. Fragment: ubiquitin. Engineered: yes. Tumor necrosis factor alpha-induced protein 3. Chain: d, f, e. Fragment: a20-type 7 zinc finger domain, residues 757-790. Synonym: tnf alpha-induced protein 3, otu domain-containing protein 7c, putative DNA-binding protein a20, zinc finger protein a20.

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: ubc. Expressed in: escherichia coli. Expression_system_taxid: 562. Gene: tnfaip3.

Resolution:

1.98Å R-factor: 0.218 R-free: 0.255

Authors:

H.Nishimasu,R.Ishitani,O.Nureki

Key ref:

F.Tokunaga et al. (2012). Specific recognition of linear polyubiquitin by A20 zinc finger 7 is involved in NF-κB regulation. Embo J, 31, 3856-3870. PubMed id: 23032187

Date:

09-Jul-12 Release date: 13-Feb-13

Protein chains

P0CG48  (UBC_HUMAN) -  Polyubiquitin-C from Homo sapiens

Seq: 685 a.a.

Struc: 76 a.a.

Protein chain

P21580  (TNAP3_HUMAN) -  Tumor necrosis factor alpha-induced protein 3 from Homo sapiens

Seq: 790 a.a.

Struc: 33 a.a.

Protein chain

P21580  (TNAP3_HUMAN) -  Tumor necrosis factor alpha-induced protein 3 from Homo sapiens

Seq: 790 a.a.

Struc: 31 a.a.

Protein chain

P21580  (TNAP3_HUMAN) -  Tumor necrosis factor alpha-induced protein 3 from Homo sapiens

Seq: 790 a.a.

Struc: 32 a.a.

Enzyme reactions

• Enzyme class 1: Chains D, F, E: E.C.2.3.2.- - ?????
• Enzyme class 2: Chains D, F, E: E.C.3.4.19.12 - ubiquitinyl hydrolase 1.
• Reaction: Thiol-dependent hydrolysis of ester, thiolester, amide, peptide and isopeptide bonds formed by the C-terminal Gly of ubiquitin (a 76-residue protein attached to proteins as an intracellular targeting signal).

Note, where more than one E.C. class is given (as above), each may correspond to a different protein domain or, in the case of polyprotein precursors, to a different mature protein.

Embo J 31:3856-3870 (2012)

PubMed id: 23032187

Specific recognition of linear polyubiquitin by A20 zinc finger 7 is involved in NF-κB regulation.

F.Tokunaga, H.Nishimasu, R.Ishitani, E.Goto, T.Noguchi, K.Mio, K.Kamei, A.Ma, K.Iwai, O.Nureki.

ABSTRACT

LUBAC (linear ubiquitin chain assembly complex) activates the canonical NF-κB pathway through linear polyubiquitination of NEMO (NF-κB essential modulator, also known as IKKγ) and RIP1. However, the regulatory mechanism of LUBAC-mediated NF-κB activation remains elusive. Here, we show that A20 suppresses LUBAC-mediated NF-κB activation by binding linear polyubiquitin via the C-terminal seventh zinc finger (ZF7), whereas CYLD suppresses it through deubiquitinase (DUB) activity. We determined the crystal structures of A20 ZF7 in complex with linear diubiquitin at 1.70-1.98 Å resolutions. The crystal structures revealed that A20 ZF7 simultaneously recognizes the Met1-linked proximal and distal ubiquitins, and that genetic mutations associated with B cell lymphomas map to the ubiquitin-binding sites. Our functional analysis indicated that the binding of A20 ZF7 to linear polyubiquitin contributes to the recruitment of A20 into a TNF receptor (TNFR) signalling complex containing LUBAC and IκB kinase (IKK), which results in NF-κB suppression. These findings provide new insight into the regulation of immune and inflammatory responses.