Carbohydrate recognition by the mannose-6-phosphate receptors.
The two P-type lectins, the 46kDa cation-dependent mannose-6-phosphate (Man-6-P) receptor (CD-MPR), and the 300kDa 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.
Department of Biochemistry, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA. jjkim@mcw.edu
Jung-Ja P
JJ
Kim
Linda J
LJ
Olson
Nancy M
NM
Dahms
D000818:Animals; D001665:Binding Sites; D050260:Carbohydrate Metabolism; D002241:Carbohydrates / Q000737:chemistry*; D006801:Humans; D008024:Ligands; D011487:Protein Conformation; D017527:Receptor, IGF Type 2 / Q000737:chemistry / Q000378:metabolism*
D002241:Carbohydrates; D008024:Ligands; D017527:Receptor, IGF Type 2