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 ◽  
...  

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.

1992 ◽  
Vol 1 (9) ◽  
pp. 709-715 ◽  
Author(s):  
R. J. Lipscombe ◽  
M. Sumiya ◽  
A. V. S. Hill ◽  
Y. L. Lau ◽  
R. J. Levinsky ◽  
...  

1998 ◽  
Vol 333 (3) ◽  
pp. 601-608 ◽  
Author(s):  
Paul G. HITCHEN ◽  
Nicholas P. MULLIN ◽  
Maureen E. TAYLOR

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.


AIDS ◽  
1999 ◽  
Vol 13 (7) ◽  
pp. 863 ◽  
Author(s):  
Antonio Amoroso ◽  
Monica Berrino ◽  
Michele Boniotto ◽  
Sergio Crovella ◽  
Elvia Palomba ◽  
...  

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