title: Structure of a C-type carbohydrate recognition domain from the macrophage mannose receptor.
abstract: The mannose receptor of macrophages and liver endothelium mediates clearance of pathogenic organisms and potentially harmful glycoconjugates. The extracellular portion of the receptor includes eight C-type carbohydrate recognition domains (CRDs), of which one, CRD-4, shows detectable binding to monosaccharide ligands. We have determined the crystal structure of CRD-4. Although the basic C-type lectin fold is preserved, a loop extends away from the core of the domain to form a domain-swapped dimer in the crystal. Of the two Ca(2+) sites, only the principal site known to mediate carbohydrate binding in other C-type lectins is occupied. This site is altered in a way that makes sugar binding impossible in the mode observed in other C-type lectins. The structure is likely to represent an endosomal form of the domain formed when Ca(2+) is lost from the auxiliary calcium site. The structure suggests a mechanism for endosomal ligand release in which the auxiliary calcium site serves as a pH sensor. Acid pH-induced removal of this Ca(2+) results in conformational rearrangements of the receptor, rendering it unable to bind carbohydrate ligands.
authors.affiliation: Department of Structural Biology, Stanford University School of Medicine, Stanford, California 94305, USA.
authors.forename: H
authors.initials: H
authors.lastname: Feinberg
authors.forename: S
authors.initials: S
authors.lastname: Park-Snyder
authors.forename: A R
authors.initials: AR
authors.lastname: Kolatkar
authors.forename: C T
authors.initials: CT
authors.lastname: Heise
authors.forename: M E
authors.initials: ME
authors.lastname: Taylor
authors.forename: W I
authors.initials: WI
authors.lastname: Weis
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002118:Calcium / Q000378:metabolism; D050260:Carbohydrate Metabolism; D018360:Crystallography, X-Ray; D006801:Humans; D006863:Hydrogen-Ion Concentration; D037102:Lectins / Q000737:chemistry; D037181:Lectins, C-Type; D008024:Ligands; D008264:Macrophages / Q000378:metabolism*; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry; D011487:Protein Conformation; D017510:Protein Folding; D017433:Protein Structure, Secondary; D051381:Rats; D011956:Receptors, Cell Surface / Q000737:chemistry* / Q000378:metabolism; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism
chemical_list: D037102:Lectins; D037181:Lectins, C-Type; D008024:Ligands; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D010446:Peptide Fragments; D011956:Receptors, Cell Surface; D011994:Recombinant Proteins; D002118:Calcium