PDBsum entry 5cw3

Metal binding protein

PDB id: 5cw3

Contents

Protein chains

248 a.a.

250 a.a.

Metals

_ZN ×2

Waters ×24

PDB id:

5cw3

Name:

Metal binding protein

Title:

Structure of cfbrcc36-cfkiaa0157 complex (zn edge)

Structure:

Brca1/brca2-containing complex subunit 3. Chain: a, c. Engineered: yes. Protein fam175b. Chain: b, d. Engineered: yes

Source:

Camponotus floridanus. Florida carpenter ant. Organism_taxid: 104421. Gene: eag_15736. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108. Gene: eag_01033. Expression_system_taxid: 7108

Resolution:

2.55Å R-factor: 0.213 R-free: 0.258

Authors:

E.Zeqiraj

Key ref:

E.Zeqiraj et al. (2015). Higher-Order Assembly of BRCC36-KIAA0157 Is Required for DUB Activity and Biological Function. Mol Cell, 59, 970-983. PubMed id: 26344097 DOI: 10.1016/j.molcel.2015.07.028

Date:

27-Jul-15 Release date: 16-Sep-15

Protein chains

E2AXC7  (BRCC3_CAMFO) -  Lys-63-specific deubiquitinase BRCC36 from Camponotus floridanus

Seq: 253 a.a.

Struc: 248 a.a.

Protein chains

E2AB17  (F175B_CAMFO) -  BRISC complex subunit FAM175B from Camponotus floridanus

Seq: 471 a.a.

Struc: 250 a.a.

Enzyme reactions

• Enzyme class: Chains A, C: E.C.3.4.19.- - ?????

DOI no: 10.1016/j.molcel.2015.07.028

Mol Cell 59:970-983 (2015)

PubMed id: 26344097

Higher-Order Assembly of BRCC36-KIAA0157 Is Required for DUB Activity and Biological Function.

E.Zeqiraj, L.Tian, C.A.Piggott, M.C.Pillon, N.M.Duffy, D.F.Ceccarelli, A.F.Keszei, K.Lorenzen, I.Kurinov, S.Orlicky, G.D.Gish, A.J.Heck, A.Guarné, R.A.Greenberg, F.Sicheri.

ABSTRACT

BRCC36 is a Zn(2+)-dependent deubiquitinating enzyme (DUB) that hydrolyzes lysine-63-linked ubiquitin chains as part of distinct macromolecular complexes that participate in either interferon signaling or DNA-damage recognition. The MPN(+) domain protein BRCC36 associates with pseudo DUB MPN(-) proteins KIAA0157 or Abraxas, which are essential for BRCC36 enzymatic activity. To understand the basis for BRCC36 regulation, we have solved the structure of an active BRCC36-KIAA0157 heterodimer and an inactive BRCC36 homodimer. Structural and functional characterizations show how BRCC36 is switched to an active conformation by contacts with KIAA0157. Higher-order association of BRCC36 and KIAA0157 into a dimer of heterodimers (super dimers) was required for DUB activity and interaction with targeting proteins SHMT2 and RAP80. These data provide an explanation of how an inactive pseudo DUB allosterically activates a cognate DUB partner and implicates super dimerization as a new regulatory mechanism underlying BRCC36 DUB activity, subcellular localization, and biological function.