Mannan-binding lectin
Encyclopedia
Mannose-binding lectin also named mannose
- or mannan
-binding protein (MBP), is an important factor in innate immunity.
s in the C-type
lectin
superfamily, whose function appears to be pattern recognition in the first line of defense in the pre-immune host.
MBL recognizes carbohydrate patterns, found on the surface of a large number of pathogenic micro-organisms, including bacteria
, viruses, protozoa
and fungi.
Binding of MBL to a micro-organism results in activation of the lectin pathway of the complement system
.
Although MBL can form several oligomeric forms, there are indications that dimers and trimers are not biologically active and at least a tetramer form is needed for activation of complement.
, the alternative pathway
, and the mannose-binding (MB) lectin pathway
. The most-recently discovered mannose-binding lectin pathway activates complement through the mannose-binding lectin protein. MBL binds to carbohydrates (to be specific, mannose and fucose residues) found on the surface of many pathogens.
For example, MBL has been show to bind to:
called MASP-2 (MBL-associated serine protease).
In order to activate the complement system when MBL binds to its target (for example, mannose on the surface of a bacterium), the MASP protein functions to cleave the blood protein C4
into C4a and C4b. The C4b fragments can then bind to the surface of the bacterium, and initiate the formation of a C3 convertase.
The subsequent complement cascade catalyzed by C3 convertase results in creating a membrane attack complex, which causes lysis of the pathogen that MBL bound to.
as a response to infection, and is part of many other factors termed acute phase protein
s.
Mannose
Mannose is a sugar monomer of the aldohexose series of carbohydrates. Mannose is a C-2 epimer of glucose. It is not part of human metabolism, but is a component of microbial cell walls, and is therefore a target of the immune system and also of antibiotics....
- or mannan
Mannan
Mannan is a plant polysaccharide that is a polymer of the sugar mannose.Detection of mannan leads to lysis in the mannan-binding lectin pathway.It is generally found in yeast, bacteria and plants. It shows α linkage. It is a form of storage polysaccharide.-See Also:Mannan Oligosaccharides...
-binding protein (MBP), is an important factor in innate immunity.
Function
MBL belongs to the class of collectinCollectin
Collectins are soluble pattern recognition receptors belonging to the superfamily of collagen containing C-type lectins.Eight collectins have been identified including mannan-binding lectin , surfactant protein A , surfactant protein D , collectin liver 1 , collectin placenta 1 , conglutinin,...
s in the C-type
C-type lectin
A C-type lectin is a type of carbohydrate-binding protein domain known as a lectin. The C-type designation is from their requirement for calcium for binding. Proteins that contain C-type lectin domains have a diverse range of functions including cell-cell adhesion, immune response to pathogens and...
lectin
Lectin
Lectins are sugar-binding proteins that are highly specific for their sugar moieties. They play a role in biological recognition phenomena involving cells and proteins. For example, some viruses use lectins to attach themselves to the cells of the host organism during infection...
superfamily, whose function appears to be pattern recognition in the first line of defense in the pre-immune host.
MBL recognizes carbohydrate patterns, found on the surface of a large number of pathogenic micro-organisms, including bacteria
Bacteria
Bacteria are a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria have a wide range of shapes, ranging from spheres to rods and spirals...
, viruses, protozoa
Protozoa
Protozoa are a diverse group of single-cells eukaryotic organisms, many of which are motile. Throughout history, protozoa have been defined as single-cell protists with animal-like behavior, e.g., movement...
and fungi.
Binding of MBL to a micro-organism results in activation of the lectin pathway of the complement system
Complement system
The complement system helps or “complements” the ability of antibodies and phagocytic cells to clear pathogens from an organism. It is part of the immune system called the innate immune system that is not adaptable and does not change over the course of an individual's lifetime...
.
Structure
MBL has an oligomeric structure (400-700 kDa), built of subunits that contain three identical peptide chains of 32 kDa each.Although MBL can form several oligomeric forms, there are indications that dimers and trimers are not biologically active and at least a tetramer form is needed for activation of complement.
Activation
The complement system can be activated through three pathways the classical pathwayClassical complement pathway
The Classical pathway of activation of the complement system is a group of blood proteins that mediate the specific antibody response. The main activators of the Classical Pathway are antigen-antibody complexes.-Initiation:...
, the alternative pathway
Alternative complement pathway
The alternative pathway of the complement system is an innate component of the immune system's natural defense against infections, which can operate without antibody participation....
, and the mannose-binding (MB) lectin pathway
Mannan-binding lectin pathway
The Mannan-binding lectin pathway is similar in structure to the classical complement pathway, in that, after activation, it proceeds through the action of C4 and C2 to produce activated complement proteins further down the cascade...
. The most-recently discovered mannose-binding lectin pathway activates complement through the mannose-binding lectin protein. MBL binds to carbohydrates (to be specific, mannose and fucose residues) found on the surface of many pathogens.
For example, MBL has been show to bind to:
- yeastYeastYeasts are eukaryotic micro-organisms classified in the kingdom Fungi, with 1,500 species currently described estimated to be only 1% of all fungal species. Most reproduce asexually by mitosis, and many do so by an asymmetric division process called budding...
s such as Candida albicansCandida albicansCandida albicans is a diploid fungus that grows both as yeast and filamentous cells and a causal agent of opportunistic oral and genital infections in humans. Systemic fungal infections including those by C... - viruses such as HIVHIVHuman immunodeficiency virus is a lentivirus that causes acquired immunodeficiency syndrome , a condition in humans in which progressive failure of the immune system allows life-threatening opportunistic infections and cancers to thrive...
and influenza A - many bacteriaBacteriaBacteria are a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria have a wide range of shapes, ranging from spheres to rods and spirals...
including SalmonellaSalmonellaSalmonella is a genus of rod-shaped, Gram-negative, non-spore-forming, predominantly motile enterobacteria with diameters around 0.7 to 1.5 µm, lengths from 2 to 5 µm, and flagella which grade in all directions . They are chemoorganotrophs, obtaining their energy from oxidation and reduction...
and Streptococci - parasites like Leishmania
Complexes
MBL in the blood is complexed with (bound to) another protein, a serine proteaseSerine protease
Serine proteases are enzymes that cleave peptide bonds in proteins, in which serine serves as the nucleophilic amino acid at the active site.They are found ubiquitously in both eukaryotes and prokaryotes...
called MASP-2 (MBL-associated serine protease).
In order to activate the complement system when MBL binds to its target (for example, mannose on the surface of a bacterium), the MASP protein functions to cleave the blood protein C4
Complement component 4
Complement component 4 is a protein involved in the complement system.It is cleaved into proteins 4a and 4b.* C4a is an anaphylatoxin.* C4b forms part of C3-convertase, in conjunction with 2a:* C4b can bind CR1....
into C4a and C4b. The C4b fragments can then bind to the surface of the bacterium, and initiate the formation of a C3 convertase.
The subsequent complement cascade catalyzed by C3 convertase results in creating a membrane attack complex, which causes lysis of the pathogen that MBL bound to.
Clinical significance
It is produced in the liverLiver
The liver is a vital organ present in vertebrates and some other animals. It has a wide range of functions, including detoxification, protein synthesis, and production of biochemicals necessary for digestion...
as a response to infection, and is part of many other factors termed acute phase protein
Acute phase protein
Acute-phase proteins are a class of proteins whose plasma concentrations increase or decrease in response to inflammation...
s.