2RLB: Crystal Structure Cation-dependent Mannose 6-phosphate Receptor At Ph 6.5 Bound To M6p In Absence Of Mn

The cation-dependent mannose 6-phosphate receptor (CD-MPR) is a key component of the lysosomal enzyme targeting system that binds newly synthesized mannose 6-phosphate (Man-6-P)-containing acid hydrolases and transports them to endosomal compartments. The interaction between the MPRs and its ligands is pH-dependent; the homodimeric CD-MPR binds lysosomal enzymes optimally in the pH environment of the trans Golgi network (pH approximately 6.5) and releases its cargo in acidic endosomal compartments (<pH 5.5) and at the cell surface. In addition, CD-MPR binding affinities are modulated by divalent cations. Our previous crystallographic studies have shown that at pH 6.5, the CD-MPR bound to Man-6-P adopts a significantly different quaternary conformation than the CD-MPR in a ligand-unbound state, a feature unique among known lectin structures. To determine whether different pH conditions elicit conformational changes in the receptor that alters ligand binding affinities, we have obtained additional crystal structures representative of the various environments encountered by the receptor including: 1) the CD-MPR bound at pH 6.5 (i.e. trans Golgi network) to a high affinity ligand (the terminally phosphorylated trisaccharide P-Man(alpha1,2)Man(alpha1,2)Man-O-(CH(2))(8)COOMe), 2) the CD-MPR at pH 4.8 in an unbound state (i.e. endosome), and 3) the CD-MPR at pH 7.4 (i.e. cell surface). A detailed comparison of the available CD-MPR structures reveals the positional invariability of specific binding pocket residues and implicates intermonomer contact(s), as well as the protonation state of Man-6-P, as regulators of pH-dependent carbohydrate binding.
PDB ID: 2RLBDownload
MMDB ID: 62385
PDB Deposition Date: 2007/10/18
Updated in MMDB: 2017/11
Experimental Method:
x-ray diffraction
Resolution: 1.75  Å
Source Organism:
Similar Structures:
Biological Unit for 2RLB: dimeric; determined by author and by software (PISA)
Molecular Components in 2RLB
Label Count Molecule
Proteins (2 molecules)
Cation-dependent Mannose-6-phosphate Receptor(Gene symbol: M6PR)
Molecule annotation
Chemicals (4 molecules)
* Click molecule labels to explore molecular sequence information.

Citing MMDB