biostudies-literatureTanner NIsrael Science FoundationE325https://www.ebi.ac.uk/biostudies/studies/S-EPMC6723200biostudies-literatureUnknown9(8)Ubiquitin (Ub) receptors respond to ubiquitylation signals. They bind ubiquitylated substrates and exert their activity in situ. Intriguingly, Ub receptors themselves undergo rapid ubiquitylation and deubiquitylation. Here we asked what is the function of ubiquitylation of Ub receptors? We focused on yeast epsin, a Ub receptor that decodes the ubiquitylation signal of plasma membrane proteins into an endocytosis response. Using mass spectrometry, we identified lysine-3 as the major ubiquitylation site in the epsin plasma membrane binding domain. By projecting this ubiquitylation site onto our crystal structure, we hypothesized that this modification would compete with phosphatidylinositol-4,5-bisphosphate (PIP₂) binding and dissociate epsin from the membrane. Using an <i>E. coliBiomoleculesRemodeling Membrane Binding by Mono-Ubiquitylation.PMC6723200464/11, 651/16, 1499/10, 1665/16, 1623/17 and 2167/17Nachman IKleifeld OPrag GTanner NfalseRemodeling Membrane Binding by Mono-Ubiquitylation.Ubiquitin (Ub) receptors respond to ubiquitylation signals. They bind ubiquitylated substrates and exert their activity in situ. Intriguingly, Ub receptors themselves undergo rapid ubiquitylation and deubiquitylation. Here we asked what is the function of ubiquitylation of Ub receptors? We focused on yeast epsin, a Ub receptor that decodes the ubiquitylation signal of plasma membrane proteins into an endocytosis response. Using mass spectrometry, we identified lysine-3 as the major ubiquitylation site in the epsin plasma membrane binding domain. By projecting this ubiquitylation site onto our crystal structure, we hypothesized that this modification would compete with phosphatidylinositol-4,5-bisphosphate (PIP₂) binding and dissociate epsin from the membrane. Using an <i>E. coli2019-01-01T00:00:00Z2019 Jul2026-04-29T15:54:12.247Z2019-09-14T07:05:43ZS-EPMC67232003137022210.3390/biom9080325