scholarly journals Orientation of sugars bound to the principal C-type carbohydrate-recognition domain of the macrophage mannose receptor

1998 ◽  
Vol 333 (3) ◽  
pp. 601-608 ◽  
Author(s):  
Paul G. HITCHEN ◽  
Nicholas P. MULLIN ◽  
Maureen E. TAYLOR
Keyword(s):  
Binding Site ◽  
Rat Liver ◽  
Binding Protein ◽  
Mannose Receptor ◽  
Tyrosine Residue ◽  
Carbohydrate Recognition ◽  
Sugar Binding ◽  
Macrophage Mannose Receptor ◽  
Mannose Binding Protein ◽  
Mannose Binding

The extracellular region of the macrophage mannose receptor, a protein involved in the innate immune response, contains eight C-type carbohydrate-recognition domains (CRDs). The fourth of these domains, CRD-4, is central to ligand binding by the receptor, and binds mannose, fucose and N-acetylglucosamine by direct ligation to Ca2+. Site-directed mutagenesis combined with NMR and molecular modelling have been used to determine the orientation of monosaccharides bound to CRD-4. Two resonances in the 1H NMR spectrum of CRD-4 that are perturbed on sugar binding are identified as a methyl proton from a leucine side chain in the core of the domain and the H-2 proton of a histidine close to the predicted sugar-binding site. The effects of mutagenesis of this histidine residue, a nearby isoleucine residue and a tyrosine residue previously shown to stack against sugars bound to CRD-4 show the absolute orientation of sugars in the binding site. N-Acetylglucosamine binds to CRD-4 of the mannose receptor in the orientation seen in crystal structures of the CRD of rat liver mannose-binding protein. Mannose binds to CRD-4 in the orientation seen in the CRD of rat serum mannose-binding protein and is rotated by 180 ° relative to GlcNAc bound to CRD-4. Interaction of the O-methyl group and C-1 of α-methyl Fuc with the tyrosine residue accounts for the strong preference of CRD-4 for this anomer of fucose. Both anomers of fucose bind to CRD-4 in the orientation seen in rat liver mannose-binding protein.

scholarly journals The human mannose-binding protein gene. Exon structure reveals its evolutionary relationship to a human pulmonary surfactant gene and localization to chromosome 10.

1989 ◽  
Vol 170 (4) ◽  
pp. 1175-1189 ◽  
Author(s):  
K Sastry ◽  
G A Herman ◽  
L Day ◽  
E Deignan ◽  
G Bruns ◽  
...  
Keyword(s):  
Binding Protein ◽  
Evolutionary Relationship ◽  
Coding Region ◽  
Carbohydrate Recognition ◽  
Chromosome 10 ◽  
Mannose Binding Protein ◽  
Mannose Binding ◽  
Binding Protein Gene ◽  
Exon Structure ◽  
Gene Exon

The human mannose-binding protein (MBP) plays a role in first line host defense against certain pathogens. It is an acute phase protein that exists in serum as a multimer of a 32-kD subunit. The NH2 terminus is rich in cysteines that mediate interchain disulphide bonds and stabilize the second collagen-like region. This is followed by a short intervening region, and the carbohydrate recognition domain is found in the COOH-terminal region. Analysis of the human MBP gene reveals that the coding region is interrupted by three introns, and all four exons appear to encode a distinct domain of the protein. It appears that the human MBP gene has evolved by recombination of an ancestral nonfibrillar collagen gene with a gene that encodes carbohydrate recognition, and is therefore similar to the human surfactant SP-A gene and the rat MBP gene. The gene for MBP is located on the long arm of chromosome 10 at 10q11.2-q21, a region that is included in the assignment for the gene for multiple endocrine neoplasia type 2A.

scholarly journals Asymmetry adjacent to the collagen-like domain in rat liver mannose-binding protein

1997 ◽  
Vol 325 (2) ◽  
pp. 391-400 ◽  
Author(s):  
Russell WALLIS ◽  
Kurt DRICKAMER
Keyword(s):  
Rat Liver ◽  
Analytical Ultracentrifugation ◽  
Binding Protein ◽  
Chinese Hamster Ovary Cells ◽  
Gel Filtration ◽  
Chinese Hamster ◽  
Microbial Pathogens ◽  
Disulphide Bonds ◽  
Mannose Binding Protein ◽  
Mannose Binding

Rat liver mannose-binding protein (MBP-C) is the smallest known member of the collectin family of animal lectins, many of which are involved in defence against microbial pathogens. It consists of an N-terminal collagen-like domain linked to C-terminal carbohydrate-recognition domains. MBP-C, overproduced in Chinese-hamster ovary cells, is post-translationally modified and processed in a manner similar to the native lectin. Analytical ultracentrifugation experiments indicate that MBP-C is trimeric, with a weight-averaged molecular mass of approx. 77 kDa. The rate of sedimentation of MBP-C and its mobility on gel filtration suggest a highly elongated molecule. Anomalous behaviour on gel filtration due to this extended conformation may explain previous suggestions that MBP-C forms a higher oligomer. The polypeptide chains of the MBP-C trimer are linked by disulphide bonds between two cysteine residues at the N-terminal junction of the collagen-like domain. Analysis of an N-terminal tryptic fragment reveals that the disulphide bonding in MBP-C is heterogeneous and asymmetrical. These results indicate that assembly of MBP-C oligomers probably proceeds in a C- to N-terminal direction: trimerization at the C-terminus is followed by assembly of the collagenous domain and finally formation of N-terminal disulphide bonds. The relatively simple organization of MBP-C provides a template for understanding larger, more complex collectins.

scholarly journals Structural Analysis of Monosaccharide Recognition by Rat Liver Mannose-binding Protein

1996 ◽  
Vol 271 (2) ◽  
pp. 663-674 ◽  
Author(s):  
Kenneth K.-S. Ng ◽  
Kurt Drickamer ◽  
William I. Weis
Keyword(s):  
Structural Analysis ◽  
Rat Liver ◽  
Binding Protein ◽  
Mannose Binding Protein ◽  
Mannose Binding

scholarly journals Trypanosoma cruzi amastigote adhesion to macrophages is facilitated by the mannose receptor.

1995 ◽  
Vol 182 (5) ◽  
pp. 1243-1258 ◽  
Author(s):  
S Kahn ◽  
M Wleklinski ◽  
A Aruffo ◽  
A Farr ◽  
D Coder ◽  
...  
Keyword(s):  
Trypanosoma Cruzi ◽  
Mammalian Cells ◽  
Binding Protein ◽  
Mannose Receptor ◽  
Host Cells ◽  
Surface Glycoprotein ◽  
Carbohydrate Binding ◽  
Mouse Tissues ◽  
Mannose Binding Protein ◽  
Mannose Binding

Trypanosoma cruzi is an obligate intracellular protozoan parasite. The mammalian stage of the parasite life cycle describes amastigotes as an intracellular form that replicates, and trypomastigotes as an extracellular form that disseminates and invades cells. Recent studies, however, have demonstrated that amastigotes circulate in the blood of infected mammals and can invade mammalian cells. In this report, a T. cruzi surface glycoprotein gene, SA85-1.1, was expressed as an immunoglobulin chimera, and this recombinant globulin was used to screen normal mouse tissues for adhesive interactions. This approach identified a subset of macrophages in the skin and peripheral lymph node that bind the T. cruzi surface glycoproteins through the mannose receptor. To further examine the T. cruzi mannose receptor carbohydrate ligands, the interaction between T. cruzi and the mannose-binding protein, a mammalian lectin with similar carbohydrate binding specificities as the mannose receptor, was examined. These studies demonstrated that the mannose-binding protein recognized amastigotes, but not trypomastigotes or epimastigotes, and suggested that amastigotes would also be recognized by the mannose receptor. Therefore, amastigote adhesion to macrophages was investigated, and these experiments demonstrated that the mannose receptor contributes to amastigote adhesion. The data identify the first mammalian lectins that bind to T. cruzi, and are involved in T. cruzi invasion of mammalian cells. The data suggest that amastigotes and trypomastigotes may have developed different mechanisms to adhere to and invade host cells. In addition, it has been established that IFN-gamma-activated macrophages express low levels of the mannose receptor and are trypanocidal; this suggests that the interaction between amastigotes and the mannose receptor enables amastigotes to increase their adherence with a population of macrophages that are nontrypanocidal and permissive for their intracellular replication.

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