Carbohydrate recognition by the mannose-6-phosphate receptors.

Carbohydrate recognition by the mannose-6-phosphate receptors.
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甘露糖-6-磷酸受体识别碳水化合物。

DOI:
10.1016/j.sbi.2009.09.002
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发表时间:
2009-10
影响因子:
6.8
通讯作者:
Dahms, Nancy M.
Dahms, Nancy M.
中科院分区:
生物学2区
文献类型:
--
作者:
Kim, Jung-Ja P.;Olson, Linda J.;Dahms, Nancy M.

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两种P型凝集素,46 kDa阳离子依赖性甘露糖6-磷酸(Man-6-P)受体(CD-MPR)和300 kDa阳离子非依赖性Man-6-P受体(CI-MPR),是不断增长的甘露糖6-磷酸受体同源(MRH)蛋白家族的创始成员。MPR的主要细胞功能是将含Man-6-P的酸性水解酶从高尔基体转运至内体/溶酶体隔室。CD-MPR和CI-MPR结构分析的最新进展揭示了这些受体识别磷酸甘露糖基的结构基础,并提供了受体如何装载和卸载其货物的见解。一个令人惊讶的发现是,CD-MPR是动态的,具有至少两个稳定的四级状态,开放(配体结合)和封闭(无配体)构象,类似于血红蛋白的构象。配体结合稳定了开放构象;细胞表面和内体区室环境pH的变化削弱了配体-受体相互作用和/或削弱了亚基界面处的静电相互作用,导致闭合构象。
The two P-type lectins, the 46 kDa cation-dependent mannose 6-phosphate (Man-6-P) receptor (CD-MPR) and the 300 kDa cation-independent Man-6-P receptor (CI-MPR), are the founding members of the growing family of mannose 6-phosphate receptor homology (MRH) proteins. A major cellular function of the MPRs is to transport Man-6-P-containing acid hydrolases from the Golgi to endosomal/lysosomal compartments. Recent advances in the structural analyses of both CD-MPR and CI-MPR have revealed the structural basis for phosphomannosyl recognition by these receptors and provided insights into how the receptors load and unload their cargo. A surprising finding is that the CD-MPR is dynamic, with at least two stable quaternary states, the open (ligand bound) and closed (ligand free) conformations, similar to those of hemoglobin. Ligand binding stabilizes the open conformation; changes in the pH of the environment at the cell surface and in endosomal compartments weaken the ligand-receptor interaction and/or weaken the electrostatic interactions at the subunit interface, resulting in the closed conformation.
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发表时间: 2000-07-18
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