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Mannose 6-phosphate receptor homology (MRH) domain-containing lectins in the secretory pathway. Biochim Biophys Acta 2011 Sep;1810(9):815-26

Date

07/05/2011

Pubmed ID

21723917

Pubmed Central ID

PMC3150748

DOI

10.1016/j.bbagen.2011.06.016

Scopus ID

2-s2.0-79960702536 (requires institutional sign-in at Scopus site)   29 Citations

Abstract

BACKGROUND: The mannose 6-phosphate receptor homology (MRH) domain-containing family of proteins, which include recycling receptors (mannose 6-phosphate receptors, MPRs), resident endoplasmic reticulum (ER) proteins (glucosidase II β-subunit, XTP3-B, OS-9), and a Golgi glycosyltransferase (GlcNAc-phosphotransferase γ-subunit), are characterized by the presence of one or more MRH domains. Many MRH domains act as lectins and bind specific phosphorylated (MPRs) or non-phosphorylated (glucosidase II β-subunit, XTP3-B and OS-9) high mannose-type N-glycans. The MPRs are the only proteins known to bind mannose 6-phosphate (Man-6-P) residues via their MRH domains.

SCOPE OF REVIEW: Recent biochemical and structural studies that have provided valuable insight into the glycan specificity and mechanisms of carbohydrate recognition by this diverse group of MRH domain-containing proteins are highlighted.

MAJOR CONCLUSIONS: Currently, three-dimensional structures are known for ten MRH domains, revealing the conservation of a similar fold. OS-9 and the MPRs use the same four residues (Gln, Arg, Glu, and Tyr) to bind mannose.

GENERAL SIGNIFICANCE: The MRH domain-containing proteins play key roles in the secretory pathway: glucosidase II, XTP3-B, and OS-9 are involved in the recognition of nascent glycoproteins, whereas the MPRs play an essential role in lysosome biogenesis by targeting Man-6-P-containing lysosomal enzymes to the lysosome.

Author List

Castonguay AC, Olson LJ, Dahms NM

Authors

Nancy M. Dahms PhD Professor in the Biochemistry department at Medical College of Wisconsin
Linda J. Olson PhD Assistant Professor in the Pharmacology and Toxicology department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Amino Acid Sequence
Animals
Humans
Lectins
Lysosomes
Mannosephosphates
Models, Molecular
Neoplasm Proteins
Polysaccharides
Protein Structure, Tertiary
Receptor, IGF Type 2
Secretory Pathway
Sequence Alignment
Substrate Specificity