6SAP

Structure of the PUB domain from Ubiquitin Regulatory X domain protein 1 (UBXD1)

Summary for 6SAP

• Entry DOI: 10.2210/pdb6sap/pdb
• NMR Information: BMRB: 27977
• Descriptor: UBX domain-containing protein 6 (1 entity in total)
• Functional Keywords: ubxd1, pub domain, p97, protein interaction, nmr solution structure, protein binding
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 1
• Total formula weight: 13822.57

Authors

Beuck, C.,Bayer, P.,Blueggel, M. (deposition date: 2019-07-17, release date: 2019-12-25, Last modification date: 2024-06-19)

Primary citation

Blueggel, M.,van den Boom, J.,Meyer, H.,Bayer, P.,Beuck, C.
Structure of the PUB Domain from Ubiquitin Regulatory X Domain Protein 1 (UBXD1) and Its Interaction with the p97 AAA+ ATPase.
Biomolecules, 9:-, 2019

PubMed Abstract: AAA+ ATPase p97/valosin-containing protein (VCP)/Cdc48 is a key player in various cellular stress responses in which it unfolds ubiquitinated proteins to facilitate their degradation by the proteasome. P97 works in different cellular processes using alternative sets of cofactors and is implicated in multiple degenerative diseases. Ubiquitin regulatory X domain protein 1 (UBXD1) has been linked to pathogenesis and is unique amongst p97 cofactors because it interacts with both termini of p97. Its N-domain binds to the N-domain and N/D1 interface of p97 and regulates its ATPase activity. The PUB (peptide:-glycanase and UBA or UBX-containing proteins) domain binds the p97 C-terminus, but how it controls p97 function is still unknown. Here we present the NMR structure of UBXD1-PUB together with binding studies, mutational analysis, and a model of UBXD1-PUB in complex with the p97 C-terminus. While the binding pocket is conserved among PUB domains, UBXD1-PUB features a unique loop and turn regions suggesting a role in coordinating interaction with downstream regulators and substrate processing.

PubMed: 31847414
DOI: 10.3390/biom9120876

Experimental method

SOLUTION NMR