Mannose-binding lectin: structure, function, genetics and disease associations.
Mannose-binding lectin (MBL), a serum protein characterised by both collagenous regions and lectin domains, plays an important role in innate immune defence. It binds to the repeating sugar arrays on many microbial surfaces through multiple lectin domains and, following binding, is able to activate the complement system via an associated serum protease, MASP-2. Serum levels of MBL are influenced by three mutations clustered in exon 1 of the gene and are further modulated by various promoter region polymorphisms. The exon 1 mutations lead to secondary structural abnormalities of the collagenous triple helix and a failure to form biologically functional higher order oligomers. There is an increased incidence of infections in individuals with such mutations and an association with the autoimmune disorders SLE and rheumatoid arthritis. Nevertheless, MBL genotyping of various populations has led to the suggestion that there may be some biological advantage associated with absence of the protein. These and other findings suggest that the concept of MBL as a protein involved solely in first line defence is an oversimplification and the protein should rather be viewed as having a range of activities including disease modulation.
Turner
M W
MW
Immunobiology Unit, Institute of Child Health, University College London, UK. m.turner@ich.ucl.ac.uk
Hamvas
R M
RM
D000210:Acute-Phase Reaction; D000483:Alleles; D017398:Alternative Splicing; D000818:Animals; D001327:Autoimmune Diseases / Q000235:genetics; D001419:Bacteria / Q000378:metabolism; D002118:Calcium / Q000502:physiology; D002352:Carrier Proteins / Q000097:blood / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D002879:Chromosomes, Human, Pair 10 / Q000235:genetics; D037222:Collectins; D003167:Complement Activation / Q000502:physiology; D004252:DNA Mutational Analysis; D005006:Ethnicity / Q000235:genetics; D056890:Eukaryota / Q000378:metabolism; D019143:Evolution, Molecular; D005091:Exons / Q000235:genetics; D005658:Fungi / Q000378:metabolism; D005787:Gene Frequency; D005796:Genes; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007239:Infections / Q000209:etiology; D046911:Macromolecular Substances; D008358:Mannose / Q000378:metabolism; D050606:Mannose-Binding Protein-Associated Serine Proteases; D018448:Models, Immunological; D008958:Models, Molecular; D009154:Mutation; D009895:Opsonin Proteins / Q000276:immunology; D011485:Protein Binding; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D012697:Serine Endopeptidases / Q000235:genetics / Q000378:metabolism; D013045:Species Specificity; D014780:Viruses / Q000378:metabolism
D002352:Carrier Proteins; D037222:Collectins; D046911:Macromolecular Substances; D009895:Opsonin Proteins; D050606:Mannose-Binding Protein-Associated Serine Proteases; D012697:Serine Endopeptidases; D008358:Mannose; D002118:Calcium