title: The HECT domain of the ubiquitin ligase Rsp5 contributes to substrate recognition.
abstract: Ubiquitin modification of endosomal membrane proteins is a signal for active inclusion into the Multivesicular Body (MVB) pathway, resulting in lysosomal degradation. However, the endosome represents a dynamic site of protein sorting with a majority of proteins destined for recycling, rather than MVB targeting. Substrate recognition by ubiquitin ligases is therefore highly regulated. We have investigated substrate recognition by the Nedd4 ortholog Rsp5 as a model for understanding ligase-substrate interactions. Rsp5 interacts directly with its substrate Cps1 via a novel interaction mode. Perturbation of this mode of interaction revealed a compensatory role for the Rsp5 adaptor Bsd2. These results highlight the ability of Rsp5 to interact with substrates via multiple modalities, suggesting additional mechanisms of regulating this interaction and relevant outcomes.
authors.affiliation: Department of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine, Rochester, Minnesota 55905, USA.
authors.forename: Jacqueline R E
authors.initials: JR
authors.lastname: Lee
authors.forename: Andrea J
authors.initials: AJ
authors.lastname: Oestreich
authors.forename: Johanna A
authors.initials: JA
authors.lastname: Payne
authors.forename: Mia S
authors.initials: MS
authors.lastname: Gunawan
authors.forename: Andrew P
authors.initials: AP
authors.lastname: Norgan
authors.forename: David J
authors.initials: DJ
authors.lastname: Katzmann
mesh_terms: D020816:Amino Acid Motifs; D002268:Carboxypeptidases / Q000235:genetics / Q000378:metabolism*; D056827:Endosomal Sorting Complexes Required for Transport / Q000235:genetics / Q000378:metabolism*; D010446:Peptide Fragments / Q000378:metabolism*; D011487:Protein Conformation; D021381:Protein Transport; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D025801:Ubiquitin / Q000378:metabolism*; D043743:Ubiquitin-Protein Ligase Complexes / Q000235:genetics / Q000378:metabolism*; D054875:Ubiquitination
chemical_list: C495386:BSD2 protein, S cerevisiae; D056827:Endosomal Sorting Complexes Required for Transport; D010446:Peptide Fragments; D029701:Saccharomyces cerevisiae Proteins; D025801:Ubiquitin; D043743:Ubiquitin-Protein Ligase Complexes; D002268:Carboxypeptidases; C019836:CPS1 protein, S cerevisiae; C469287:RSP5 protein, S cerevisiae