PDBsum entry 2pop

Signaling protein/apoptosis

PDB id: 2pop

Contents

Protein chains

326 a.a. *

79 a.a. *

80 a.a. *

Metals

_ZN ×2

* Residue conservation analysis

PDB id:

2pop

Name:

Signaling protein/apoptosis

Title:

The crystal structure of tab1 and bir1 complex

Structure:

Mitogen-activated protein kinase kinase kinase 7- interacting protein 1. Chain: a, c. Fragment: n-terminal pp2c-like domain, residues 1-370. Synonym: tgf-beta-activated kinase 1 and map3k7-binding protein 1, tgf-beta-activated kinase 1-binding protein 1,tak1-binding protein 1. Engineered: yes. Mutation: yes. Baculoviral iap repeat-containing protein 4.

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: tab1, map3k7ip1. Expressed in: escherichia coli k12. Expression_system_taxid: 83333. Gene: xiap, api3, birc4, iap3.

Resolution:

3.10Å R-factor: 0.209 R-free: 0.254

Authors:

S.C.Lin

Key ref:

M.Lu et al. (2007). XIAP induces NF-kappaB activation via the BIR1/TAB1 interaction and BIR1 dimerization. Mol Cell, 26, 689-702. PubMed id: 17560374 DOI: 10.1016/j.molcel.2007.05.006

Date:

27-Apr-07 Release date: 03-Jul-07

Protein chains

Q15750  (TAB1_HUMAN) -  TGF-beta-activated kinase 1 and MAP3K7-binding protein 1 from Homo sapiens

Seq: 504 a.a.

Struc: 326 a.a.*

Protein chain

P98170  (XIAP_HUMAN) -  E3 ubiquitin-protein ligase XIAP from Homo sapiens

Seq: 497 a.a.

Struc: 79 a.a.

Protein chain

P98170  (XIAP_HUMAN) -  E3 ubiquitin-protein ligase XIAP from Homo sapiens

Seq: 497 a.a.

Struc: 80 a.a.

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

Enzyme reactions

• Enzyme class: Chains B, D: 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.2007.05.006

Mol Cell 26:689-702 (2007)

PubMed id: 17560374

XIAP induces NF-kappaB activation via the BIR1/TAB1 interaction and BIR1 dimerization.

M.Lu, S.C.Lin, Y.Huang, Y.J.Kang, R.Rich, Y.C.Lo, D.Myszka, J.Han, H.Wu.

ABSTRACT

In addition to caspase inhibition, X-linked inhibitor of apoptosis (XIAP) induces NF-kappaB and MAP kinase activation during TGF-b and BMP receptor signaling and upon overexpression. Here we show that the BIR1 domain of XIAP, which has no previously ascribed function, directly interacts with TAB1 to induce NF-kappaB activation. TAB1 is an upstream adaptor for the activation of the kinase TAK1, which in turn couples to the NF-kappaB pathway. We report the crystal structures of BIR1, TAB1, and the BIR1/TAB1 complex. The BIR1/TAB1 structure reveals a striking butterfly-shaped dimer and the detailed interaction between BIR1 and TAB1. Structure-based mutagenesis and knockdown of TAB1 show unambiguously that the BIR1/TAB1 interaction is crucial for XIAP-induced TAK1 and NF-kappaB activation. We show that although not interacting with BIR1, Smac, the antagonist for caspase inhibition by XIAP, also inhibits the XIAP/TAB1 interaction. Disruption of BIR1 dimerization abolishes XIAP-mediated NF-kappaB activation, implicating a proximity-induced mechanism for TAK1 activation.

Selected figure(s)

Figure 1.
Figure 1. Biochemical Analysis of the Interaction between the BIR1 Domain of XIAP and the N-Terminal Domain of TAB1
(A) Comigration of BIR1 and TAB1 N-terminal domain on gel filtration chromatography.
(B) Duplicate responses (left) and isotherms (right) for a 2-fold dilution series (0.143–18.25 μM) of TAB1 binding to surface-tethered BIR1 in an SPR experiment.
(C) Duplicate responses (left) and isotherms (right) for a 2-fold dilution series (0.143–18.25 μM) of TAB1 binding to surface-tethered BIR1-3 in an SPR experiment.

Figure 5.
Figure 5. TAB1 Does Not Have Phosphatase Activity
(A) Superposition of human TAB1 (yellow), human phosphatase PP2Cα (green), and bacterial phosphatase PstP (pink).
(B) Superposition of the active sites of TAB1 (yellow) and PP2Cα (green). Two metal ions and one phosphate ion are bound at the PP2Cα active site. Residues important for metal ion coordination and catalysis are labeled in black for TAB1 and green for PP2Cα.
(C) Only one Mn^2+ ion is bound at the TAB1 active site when soaked with MnCl[2]. The F[o] − F[c] map is shown at 10σ level.
(D) Electrostatic surface of the PP2Cα active site. The location of the bound phosphate ion is shown.
(E) Electrostatic surface of the same region in TAB1.

The above figures are reprinted by permission from Cell Press: Mol Cell (2007, 26, 689-702) copyright 2007.

Figures were selected by an automated process.