6sap
From Proteopedia
Structure of the PUB domain from Ubiquitin Regulatory X domain protein 1 (UBXD1)
Structural highlights
FunctionUBXN6_HUMAN May negatively regulate the ATPase activity of VCP, an ATP-driven segregase that associates with different cofactors to control a wide variety of cellular processes (PubMed:26475856). As a cofactor of VCP, it may play a role in the transport of CAV1 to lysosomes for degradation (PubMed:21822278, PubMed:23335559). It may also play a role in endoplasmic reticulum-associated degradation (ERAD) of misfolded proteins (PubMed:19275885). Together with VCP and other cofactors, it may play a role in macroautophagy, regulating for instance the clearance of damaged lysosomes (PubMed:27753622).[1] [2] [3] [4] [5] Publication Abstract from PubMedAAA+ 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:N-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. Structure of the PUB Domain from Ubiquitin Regulatory X Domain Protein 1 (UBXD1) and Its Interaction with the p97 AAA+ ATPase.,Blueggel M, van den Boom J, Meyer H, Bayer P, Beuck C Biomolecules. 2019 Dec 14;9(12). pii: biom9120876. doi: 10.3390/biom9120876. PMID:31847414[6] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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