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

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Wang, R; Qi, X; Schmiege, P; Coutavas, E; Li, X

Published Date

  • February 2020

Published In

Volume / Issue

  • 6 / 7

Start / End Page

  • eaaz1466 -

PubMed ID

  • 32095534

Pubmed Central ID

  • PMC7015683

Electronic International Standard Serial Number (EISSN)

  • 2375-2548

Digital Object Identifier (DOI)

  • 10.1126/sciadv.aaz1466


  • eng

Conference Location

  • United States