6V02

N-terminal 5 domains of CI-MPR

6V02 の概要

• エントリーDOI: 10.2210/pdb6v02/pdb
• 関連するPDBエントリー: 6P8I
• 分子名称: Cation-independent mannose-6-phosphate receptor, 2-acetamido-2-deoxy-beta-D-glucopyranose (3 entities in total)
• 機能のキーワード: lectin, receptor, protein transport, 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: 81421.01

構造登録者

Olson, L.J.,Dahms, N.M.,Kim, J.-J.P. (登録日: 2019-11-18, 公開日: 2020-09-30, 最終更新日: 2024-10-16)

主引用文献

Olson, L.J.,Misra, S.K.,Ishihara, M.,Battaile, K.P.,Grant, O.C.,Sood, A.,Woods, R.J.,Kim, J.P.,Tiemeyer, M.,Ren, G.,Sharp, J.S.,Dahms, N.M.
Allosteric regulation of lysosomal enzyme recognition by the cation-independent mannose 6-phosphate receptor.
Commun Biol, 3:498-498, 2020

PubMed Abstract: The cation-independent mannose 6-phosphate receptor (CI-MPR, IGF2 receptor or CD222), is a multifunctional glycoprotein required for normal development. Through the receptor's ability to bind unrelated extracellular and intracellular ligands, it participates in numerous functions including protein trafficking, lysosomal biogenesis, and regulation of cell growth. Clinically, endogenous CI-MPR delivers infused recombinant enzymes to lysosomes in the treatment of lysosomal storage diseases. Although four of the 15 domains comprising CI-MPR's extracellular region bind phosphorylated glycans on lysosomal enzymes, knowledge of how CI-MPR interacts with ~60 different lysosomal enzymes is limited. Here, we show by electron microscopy and hydroxyl radical protein footprinting that the N-terminal region of CI-MPR undergoes dynamic conformational changes as a consequence of ligand binding and different pH conditions. These data, coupled with X-ray crystallography, surface plasmon resonance and molecular modeling, allow us to propose a model explaining how high-affinity carbohydrate binding is achieved through allosteric domain cooperativity.

PubMed: 32908216
DOI: 10.1038/s42003-020-01211-w

実験手法

X-RAY DIFFRACTION (2.46 Å)