6Z32
Human cation-independent mannose 6-phosphate/IGF2 receptor domains 7-11
Summary for 6Z32
| Entry DOI | 10.2210/pdb6z32/pdb |
| Descriptor | Cation-independent mannose-6-phosphate receptor, alpha-D-mannopyranose-(1-2)-alpha-D-mannopyranose-(1-2)-alpha-D-mannopyranose-(1-3)-beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, SULFATE ION, ... (4 entities in total) |
| Functional Keywords | cation-independent mannose 6-phosphate receptor, insulin-like growth factor 2 receptor, mannose 6-phosphate, sugar binding protein |
| Biological source | Homo sapiens (Human) |
| Total number of polymer chains | 2 |
| Total formula weight | 164571.49 |
| Authors | Bochel, A.J.,Williams, C.,McCoy, A.J.,Hoppe, H.,Winter, A.J.,Nicholls, R.D.,Harlos, K.,Jones, Y.E.,Berger, I.,Hassan, B.,Crump, M.P. (deposition date: 2020-05-19, release date: 2020-08-19, Last modification date: 2024-01-24) |
| Primary citation | Bochel, A.J.,Williams, C.,McCoy, A.J.,Hoppe, H.J.,Winter, A.J.,Nicholls, R.D.,Harlos, K.,Jones, E.Y.,Berger, I.,Hassan, A.B.,Crump, M.P. Structure of the Human Cation-Independent Mannose 6-Phosphate/IGF2 Receptor Domains 7-11 Uncovers the Mannose 6-Phosphate Binding Site of Domain 9. Structure, 28:1300-1312.e5, 2020 Cited by PubMed Abstract: The cation-independent mannose 6-phosphate (M6P)/Insulin-like growth factor-2 receptor (CI-MPR/IGF2R) is an ∼300 kDa transmembrane protein responsible for trafficking M6P-tagged lysosomal hydrolases and internalizing IGF2. The extracellular region of the CI-MPR has 15 homologous domains, including M6P-binding domains (D) 3, 5, 9, and 15 and IGF2-binding domain 11. We have focused on solving the first structures of human D7-10 within two multi-domain constructs, D9-10 and D7-11, and provide the first high-resolution description of the high-affinity M6P-binding D9. Moreover, D9 stabilizes a well-defined hub formed by D7-11 whereby two penta-domains intertwine to form a dimeric helical-type coil via an N-glycan bridge on D9. Remarkably the D7-11 structure matches an IGF2-bound state of the receptor, suggesting this may be an intrinsically stable conformation at neutral pH. Interdomain clusters of histidine and proline residues may impart receptor rigidity and play a role in structural transitions at low pH. PubMed: 32877646DOI: 10.1016/j.str.2020.08.002 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (3.47 Å) |
Structure validation
Download full validation report
