6JWJ

Npl4 in complex with Ufd1

Summary for 6JWJ

• Entry DOI: 10.2210/pdb6jwj/pdb
• Descriptor: Nuclear protein localization protein 4, Peptide from Ubiquitin fusion degradation protein 1, ZINC ION, ... (5 entities in total)
• Functional Keywords: ubiquitin, protein binding
• Biological source: Saccharomyces cerevisiae S288C (Baker's yeast); More
• Total number of polymer chains: 2
• Total formula weight: 57427.12

Authors

Sato, Y.,Fukai, S. (deposition date: 2019-04-20, release date: 2019-12-25, Last modification date: 2023-11-22)

Primary citation

Sato, Y.,Tsuchiya, H.,Yamagata, A.,Okatsu, K.,Tanaka, K.,Saeki, Y.,Fukai, S.
Structural insights into ubiquitin recognition and Ufd1 interaction of Npl4.
Nat Commun, 10:5708-5708, 2019

PubMed Abstract: Npl4 is likely to be the most upstream factor recognizing Lys48-linked polyubiquitylated substrates in the proteasomal degradation pathway in yeast. Along with Ufd1, Npl4 forms a heterodimer (UN), and functions as a cofactor for the Cdc48 ATPase. Here, we report the crystal structures of yeast Npl4 in complex with Lys48-linked diubiquitin and with the Npl4-binding motif of Ufd1. The distal and proximal ubiquitin moieties of Lys48-linked diubiquitin primarily interact with the C-terminal helix and N-terminal loop of the Npl4 C-terminal domain (CTD), respectively. Mutational analysis suggests that the CTD contributes to linkage selectivity and initial binding of ubiquitin chains. Ufd1 occupies a hydrophobic groove of the Mpr1/Pad1 N-terminal (MPN) domain of Npl4, which corresponds to the catalytic groove of the MPN domain of JAB1/MPN/Mov34 metalloenzyme (JAMM)-family deubiquitylating enzyme. This study provides important structural insights into the polyubiquitin chain recognition by the Cdc48-UN complex and its assembly.

PubMed: 31836717
DOI: 10.1038/s41467-019-13697-y

Experimental method

X-RAY DIFFRACTION (1.58 Å)