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TitleMarked structural rearrangement of mannose 6-phosphate/IGF2 receptor at different pH environments.
Journal, issue, pagesSci Adv, Vol. 6, Issue 7, Page eaaz1466, Year 2020
Publish dateFeb 12, 2020
AuthorsRong Wang / Xiaofeng Qi / Philip Schmiege / Elias Coutavas / Xiaochun Li /
PubMed AbstractMany 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 ...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.
External linksSci Adv / PubMed:32095534 / PubMed Central
MethodsEM (single particle)
Resolution3.46 - 4.32 Å
Structure data

20815

6um1

EMDB-20815, PDB-6um1:
Structure of M-6-P/IGFII Receptor at pH 4.5
Method: EM (single particle) / Resolution: 3.46 Å

20816

6um2

EMDB-20816, PDB-6um2:
Structure of M-6-P/IGFII Receptor and IGFII complex
Method: EM (single particle) / Resolution: 4.32 Å

Chemicals

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose

Source
  • bos taurus (cattle)
  • Bovine (cattle)
  • homo sapiens (human)
KeywordsSUGAR BINDING PROTEIN / M-6-P / IGFII / receptor

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