Mannan-binding lectin

Mannan-binding lectin
Mannose-binding lectin (protein C) 2, soluble

PDB rendering based on 1hup.
Identifiers
Symbols MBL2; COLEC1; HSMBPC; MBL; MBP; MBP-C; MBP1; MGC116832; MGC116833
External IDs OMIM154545 MGI96924 HomoloGene110436 GeneCards: MBL2 Gene
RNA expression pattern
PBB GE MBL2 207256 at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 4153 17195
Ensembl ENSG00000165471 ENSMUSG00000024863
UniProt P11226 Q3UEK1
RefSeq (mRNA) NM_000242.2 NM_010776.1
RefSeq (protein) NP_000233.1 NP_034906.1
Location (UCSC) Chr 10:
54.53 – 54.53 Mb
Chr 19:
30.31 – 30.31 Mb
PubMed search [1] [2]

Mannose-binding lectin (MBL), also named mannose- or mannan-binding protein (MBP), is an important factor in innate immunity.[1][2]

Contents

Function

MBL belongs to the class of collectins 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.

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.[3]

Activation

The complement system can be activated through three pathways the classical pathway, 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:

Complexes

MBL in the blood is complexed with (bound to) another protein, a serine protease 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.

Clinical significance

It is produced in the liver as a response to infection, and is part of many other factors termed acute phase proteins.[6]

External links

References

  1. ^ Fraser IP, Koziel H, Ezekowitz RA (1998). "The serum mannose-binding protein and the macrophage mannose receptor are pattern recognition molecules that link innate and adaptive immunity.". Semin. Immunol. 10 (5): 363–72. doi:10.1006/smim.1998.0141. PMID 9799711. 
  2. ^ Worthley DL, Bardy PG, Mullighan CG (2005). "Mannose-binding lectin: biology and clinical implications.". Internal medicine journal 35 (9): 548–55. doi:10.1111/j.1445-5994.2005.00908.x. PMID 16105157. 
  3. ^ Sheriff S, Chang CY, Ezekowitz RA (November 1994). "Human mannose-binding protein carbohydrate recognition domain trimerizes through a triple alpha-helical coiled-coil". Nat. Struct. Biol. 1 (11): 789–94. doi:10.1038/nsb1194-789. PMID 7634089. 
  4. ^ de Jong MA, Vriend LE, Theelen B, Taylor ME, Fluitsma D, Boekhout T, Geijtenbeek TB (March 2010). "C-type lectin Langerin is a beta-glucan receptor on human Langerhans cells that recognizes opportunistic and pathogenic fungi". Mol. Immunol. 47 (6): 1216–25. doi:10.1016/j.molimm.2009.12.016. PMC 2837148. PMID 20097424. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2837148. 
  5. ^ Ji X, Gewurz H, Spear GT (February 2005). "Mannose binding lectin (MBL) and HIV". Mol. Immunol. 42 (2): 145–52. doi:10.1016/j.molimm.2004.06.015. PMID 15488604. 
  6. ^ Worthley DL, Bardy PG, Gordon DL, Mullighan CG (October 2006). "Mannose-binding lectin and maladies of the bowel and liver". World J. Gastroenterol. 12 (40): 6420–8. PMID 17072973. 

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