PDBsum entry 3b0f

Protein binding

PDB id: 3b0f

Contents

Protein chains

43 a.a.

Ligands

SO4

Waters ×77

PDB id:

3b0f

Name:

Protein binding

Title:

Crystal structure of the uba domain of p62 and its interaction with ubiquitin

Structure:

Sequestosome-1. Chain: a, b. Fragment: uba domain (unp residues 391-438). Synonym: stone14, ubiquitin-binding protein p62. Engineered: yes

Source:

Mus musculus. Mouse. Organism_taxid: 10090. Gene: sqstm1, a170, stap. Expressed in: escherichia coli. Expression_system_taxid: 562.

Resolution:

1.40Å R-factor: 0.172 R-free: 0.201

Authors:

S.Isogai,D.Morimoto,K.Arita,S.Unzai,T.Tenno,J.Hasegawa,Y.Sou, M.Komatsu,K.Tanaka,M.Shirakawa,H.Tochio

Key ref:

S.Isogai et al. (2011). Crystal structure of the ubiquitin-associated (UBA) domain of p62 and its interaction with ubiquitin. J Biol Chem, 286, 31864-31874. PubMed id: 21715324

Date:

09-Jun-11 Release date: 29-Jun-11

Protein chains

Q64337  (SQSTM_MOUSE) -  Sequestosome-1 from Mus musculus

Seq: 442 a.a.

Struc: 43 a.a.

J Biol Chem 286:31864-31874 (2011)

PubMed id: 21715324

Crystal structure of the ubiquitin-associated (UBA) domain of p62 and its interaction with ubiquitin.

S.Isogai, D.Morimoto, K.Arita, S.Unzai, T.Tenno, J.Hasegawa, Y.S.Sou, M.Komatsu, K.Tanaka, M.Shirakawa, H.Tochio.

ABSTRACT

p62/SQSTM1/A170 is a multimodular protein that is found in ubiquitin-positive inclusions associated with neurodegenerative diseases. Recent findings indicate that p62 mediates the interaction between ubiquitinated proteins and autophagosomes, leading these proteins to be degraded via the autophagy-lysosomal pathway. This ubiquitin-mediated selective autophagy is thought to begin with recognition of the ubiquitinated proteins by the C-terminal ubiquitin-associated (UBA) domain of p62. We present here the crystal structure of the UBA domain of mouse p62 and the solution structure of its ubiquitin-bound form. The p62 UBA domain adopts a novel dimeric structure in crystals, which is distinctive from those of other UBA domains. NMR analyses reveal that in solution the domain exists in equilibrium between the dimer and monomer forms, and binding ubiquitin shifts the equilibrium toward the monomer to form a 1:1 complex between the UBA domain and ubiquitin. The dimer-to-monomer transition is associated with a structural change of the very C-terminal end of the p62 UBA domain, although the UBA fold itself is essentially maintained. Our data illustrate that dimerization and ubiquitin binding of the p62 UBA domain are incompatible with each other. These observations reveal an autoinhibitory mechanism in the p62 UBA domain and suggest that autoinhibition plays a role in the function of p62.