7WWQ

Crystal structure of human Ufd1-Npl4 complex

Summary for 7WWQ

• Entry DOI: 10.2210/pdb7wwq/pdb
• Descriptor: Nuclear protein localization protein 4 homolog, Ubiquitin recognition factor in ER-associated degradation protein 1 (3 entities in total)
• Functional Keywords: p97, ufd1, npl4, edoplasmid reticulum-associated degradation, ubiquitin, protein binding
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 2
• Total formula weight: 54755.72

Authors

Nguyen, T.Q.,Le, L.T.M.,Kim, D.H.,Ko, K.S.,Lee, H.T.,Nguyen, Y.T.K.,Kim, H.S.,Han, B.W.,Kang, W.,Yang, J.K. (deposition date: 2022-02-14, release date: 2022-09-21, Last modification date: 2024-05-29)

Primary citation

Nguyen, T.Q.,My Le, L.T.,Kim, D.H.,Ko, K.S.,Lee, H.T.,Kim Nguyen, Y.T.,Kim, H.S.,Han, B.W.,Kang, W.,Yang, J.K.
Structural basis for the interaction between human Npl4 and Npl4-binding motif of human Ufd1.
Structure, 30:1530-1537.e3, 2022

PubMed Abstract: The heterodimer of human ubiquitin fusion degradation 1 (hUfd1) and human nuclear protein localization 4 (hNpl4) is a major cofactor of human p97 adenosine triphosphatase (ATPase). The p97-Ufd1-Npl4 complex translocates the ubiquitin-conjugated proteins from the endoplasmic reticulum membrane to the cytoplasm. Ubiquitinated proteins are then degraded by the proteasome. The structures of Npl4 and Ufd1-Npl4 (UN) complex in Saccharomyces cerevisiae have been recently reported; however, the structures of hNpl4 and the human UN complex remain unknown. Here, we report the crystal structures of the human UN complex at a resolution of 2.7 Å and hNpl4 at a resolution of 3.0 Å. We also present atomic details and characterization of the human UN complex. Crystallographic studies and site-directed mutagenesis of the hUfd1 residues involved in the interaction with hNpl4 revealed the atomic details of the two proteins.

PubMed: 36087575
DOI: 10.1016/j.str.2022.08.005

Experimental method

X-RAY DIFFRACTION (2.72 Å)