PDBsum entry 2kvb

Protein transport

PDB id: 2kvb

Contents

Protein chain

148 a.a. *

* Residue conservation analysis

PDB id:

2kvb

Name:

Protein transport

Title:

Solution structure of ci-mpr domain 5 bound to n-acetylglucosaminyl 6- phosphomethylmannoside

Structure:

Cation-independent mannose-6-phosphate receptor. Chain: a. Fragment: ci-mpr_domain5. Synonym: ci man-6-p receptor, ci-mpr, m6pr, insulin-like growth factor 2 receptor, insulin-like growth factor ii receptor, igf-ii receptor, 300 kda mannose 6-phosphate receptor, mpr 300. Engineered: yes

Source:

Bos taurus. Bovine. Organism_taxid: 9913. Gene: igf2r, m6p. Expressed in: pichia pastoris. Expression_system_taxid: 4922.

NMR struc:

20 models

Authors:

L.J.Olson,F.C.Peterson,B.F.Volkman,N.M.Dahms

Key ref:

L.J.Olson et al. (2010). Structural basis for recognition of phosphodiester-containing lysosomal enzymes by the cation-independent mannose 6-phosphate receptor. Proc Natl Acad Sci U S A, 107, 12493-12498. PubMed id: 20615935

Date:

10-Mar-10 Release date: 07-Jul-10

Protein chain

P08169  (MPRI_BOVIN) -  Cation-independent mannose-6-phosphate receptor from Bos taurus

Seq: 2499 a.a.

Struc: 148 a.a.*

* PDB and UniProt seqs differ at 4 residue positions (black crosses)

Proc Natl Acad Sci U S A 107:12493-12498 (2010)

PubMed id: 20615935

Structural basis for recognition of phosphodiester-containing lysosomal enzymes by the cation-independent mannose 6-phosphate receptor.

L.J.Olson, F.C.Peterson, A.Castonguay, R.N.Bohnsack, M.Kudo, R.R.Gotschall, W.M.Canfield, B.F.Volkman, N.M.Dahms.

ABSTRACT

Mannose 6-phosphate (Man-6-P)-dependent trafficking is vital for normal development. The biogenesis of lysosomes, a major cellular site of protein, carbohydrate, and lipid catabolism, depends on the 300-kDa cation-independent Man-6-P receptor (CI-MPR) that transports newly synthesized acid hydrolases from the Golgi. The CI-MPR recognizes lysosomal enzymes bearing the Man-6-P modification, which arises by the addition of GlcNAc-1-phosphate to mannose residues and subsequent removal of GlcNAc by the uncovering enzyme (UCE). The CI-MPR also recognizes lysosomal enzymes that elude UCE maturation and instead display the Man-P-GlcNAc phosphodiester. This ability of the CI-MPR to target phosphodiester-containing enzymes ensures lysosomal delivery when UCE activity is deficient. The extracellular region of the CI-MPR is comprised of 15 repetitive domains and contains three distinct Man-6-P binding sites located in domains 3, 5, and 9, with only domain 5 exhibiting a marked preference for phosphodiester-containing lysosomal enzymes. To determine how the CI-MPR recognizes phosphodiesters, the structure of domain 5 was determined by NMR spectroscopy. Although domain 5 contains only three of the four disulfide bonds found in the other seven domains whose structures have been determined to date, it adopts the same fold consisting of a flattened beta-barrel. Structure determination of domain 5 bound to N-acetylglucosaminyl 6-phosphomethylmannoside, along with mutagenesis studies, revealed the residues involved in diester recognition, including Y679. These results show the mechanism by which the CI-MPR recognizes Man-P-GlcNAc-containing ligands and provides new avenues to investigate the role of phosphodiester-containing lysosomal enzymes in the biogenesis of lysosomes.