@article {Yip2022,
	title = {Mechanism of client selection by the protein quality-control factor UBE2O},
	journal = {Nature Structural \& Molecular Biology},
	year = {2022},
	month = {Aug},
	abstract = {The E2/E3 enzyme UBE2O ubiquitylates diverse clients to mediate important processes, including targeting unassembled {\textquoteleft}orphan{\textquoteright} proteins for quality control and clearing ribosomes during erythropoiesis. How quality-control factors, such as UBE2O, select clients on the basis of heterogeneous features is largely unknown. Here, we show that UBE2O client selection is regulated by ubiquitin binding and a cofactor, NAP1L1. Attaching a single ubiquitin onto a client enhances UBE2O binding and multi-mono-ubiquitylation. UBE2O also repurposes the histone chaperone NAP1L1 as an adapter to recruit a subset of clients. Cryo-EM structures of human UBE2O in complex with NAP1L1 reveal a malleable client recruitment interface that is autoinhibited by the intrinsically reactive UBC domain. Adding a ubiquitylated client identifies a distinct ubiquitin-binding SH3-like domain required for client selection. Our findings reveal how multivalency and a feed-forward mechanism drive the selection of protein quality-control clients.},
	issn = {1545-9985},
	doi = {10.1038/s41594-022-00807-6},
	url = {https://doi.org/10.1038/s41594-022-00807-6},
	author = {Yip, Matthew C. J. and Sedor, Samantha F. and Shao, Sichen}
}
