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Marked structural rearrangement of mannose 6-phosphate/IGF2 receptor at different pH environments

dc.contributor.author Coutavas, Elias
dc.contributor.author Wang, Rong
dc.contributor.author Qi, Xiaofeng
dc.contributor.author Schmiege, Philip
dc.contributor.author Coutavas, Elias
dc.contributor.author Li, Xiaochun
dc.date.accessioned 2020-02-13T20:46:48Z
dc.date.available 2020-02-13T20:46:48Z
dc.date.issued 2020-02
dc.identifier.issn 2375-2548
dc.identifier.uri https://hdl.handle.net/10161/20157
dc.description.abstract <jats:p>Many cell surface receptors internalize their ligands and deliver them to endosomes, where the acidic pH causes the ligand to dissociate. The liberated receptor returns to the cell surface in a process called receptor cycling. The structural basis for pH-dependent ligand dissociation is not well understood. In some receptors, the ligand binding domain is composed of multiple repeated sequences. The insulin-like growth factor 2 receptor (IGF2R) contains 15 β strand–rich repeat domains. The overall structure and the mechanism by which IGF2R binds IGF2 and releases it are unknown. We used cryo-EM to determine the structures of the IGF2R at pH 7.4 with IGF2 bound and at pH 4.5 in the ligand-dissociated state. The results reveal different arrangements of the receptor in different pH environments mediated by changes in the interactions between the repeated sequences. These results have implications for our understanding of ligand release from receptors in endocytic compartments.</jats:p>
dc.language en
dc.publisher American Association for the Advancement of Science (AAAS)
dc.relation.ispartof Science Advances
dc.relation.isversionof 10.1126/sciadv.aaz1466
dc.title Marked structural rearrangement of mannose 6-phosphate/IGF2 receptor at different pH environments
dc.type Journal article
duke.contributor.id Coutavas, Elias|1029255
dc.date.updated 2020-02-13T20:46:47Z
pubs.begin-page eaaz1466
pubs.end-page eaaz1466
pubs.issue 7
pubs.organisational-group School of Medicine
pubs.organisational-group Medicine, Pulmonary, Allergy, and Critical Care Medicine
pubs.organisational-group Duke
pubs.organisational-group Medicine
pubs.organisational-group Clinical Science Departments
pubs.publication-status Published
pubs.volume 6
duke.contributor.orcid Coutavas, Elias|0000-0003-4904-0081


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