@article {3150160,
	title = {The Cdc48 N-terminal domain has a molecular switch that mediates the Npl4-Ufd1-Cdc48 complex formation},
	year = {2023},
	month = {2023/06/12/},
	abstract = {SummaryCdc48 (VCP/p97) is a major AAA-ATPase involved in protein quality control, along with its canonical cofactors Ufd1 and Npl4 (UN). Here, we present novel structural insights into the interactions within the Cdc48-Npl4-Ufd1 ternary complex. Using integrative modeling, we combine subunit structures with crosslinking mass spectrometry (XL-MS) to map the interaction between Npl4 and Ufd1, alone and in complex with Cdc48. We describe the stabilization of the UN assembly upon binding with the N-terminal-domain (NTD) of Cdc48 and identify a highly conserved cysteine, C115, at the Cdc48-Npl4-binding interface which is central to the stability of the Cdc48-Npl4-Ufd1 complex. Mutation of Cys115 to serine disrupts the interaction between Cdc48-NTD and Npl4-Ufd1 and leads to a moderate decrease in cellular growth and protein quality control in yeast. Our results provide structural insight into the architecture of the Cdc48-Npl4-Ufd1 complex as well as its in~vivo implications.
},
	keywords = {CDC48, CL-MS, crosslinking coupled with MS (XL-MS), integrative modeling, NPL4, protein quality control, structural mass spectrometry, UFD1},
	isbn = {0969-2126},
	url = {https://www.sciencedirect.com/science/article/pii/S0969212623001697},
	author = {Oppenheim, Tal and Radzinski, Meytal and Braitbard, Merav and Brielle, Esther S. and Yogev, Ohad and Goldberger, Eliya and Yesharim, Yarden and Ravid, Tommer and Schneidman-Duhovny, Dina and Reichmann, Dana}
}
