6Z30

Human cation-independent mannose 6-phosphate/ IGF2 receptor domains 9-10

6Z30 の概要

• エントリーDOI: 10.2210/pdb6z30/pdb
• 分子名称: Cation-independent mannose-6-phosphate receptor, alpha-D-mannopyranose-(1-3)-alpha-D-mannopyranose-(1-6)-[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 (3 entities in total)
• 機能のキーワード: mannose 6-phosphate, cation-independent mannose 6-phosphate receptor, insulin-like growth factor 2 receptor, p-type lectin, sugar binding protein
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 34719.72

構造登録者

Bochel, A.J.,Williams, C.,Crump, M.P. (登録日: 2020-05-19, 公開日: 2020-08-19, 最終更新日: 2024-11-20)

主引用文献

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

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: 32877646
DOI: 10.1016/j.str.2020.08.002

実験手法

X-RAY DIFFRACTION (1.5 Å)