Mannan-binding lectin
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| Mannose-binding lectin (protein C) 2, soluble (opsonic defect)
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| Image:PBB Protein MBL2 image.jpg | ||||||||||||||||||||||||||||||||||||||
| PDB rendering based on 1hup. | ||||||||||||||||||||||||||||||||||||||
| Available structures: For the file format that describes the 3D structures of molecules found in the Protein Data Bank, see Protein Data Bank (file format).
The Protein Data Bank (PDB) is a repository for 3-D structural data of proteins and nucleic acids. These data, typically obtained by X-ray crystallography or NMR spectroscopy, are submitted by biologists and biochemists from around the world, are released into the public domain, and can be accessed for free. HistoryFounded in 1971 by Drs. Edgar Meyer and Walter Hamilton Brookhaven National Laboratory, management of the Protein Data Bank was transferred in 1998 to members of the Research Collaboratory for Structural Bioinformatics (RCSB). The Worldwide Protein Data Bank (wwPDB) consists of organizations that act as deposition, data processing and distribution centers for PDB data. The founding members are RCSB PDB (USA), MSD-EBI (Europe) and PDBj (Japan). The BMRB (USA) group joined the wwPDB in 2006. The mission of the wwPDB is to maintain a single Protein Data Bank Archive of macromolecular structural data that is freely and publicly available to the global community. The PDB is a key resource in structural biology and is critical to more recent work in structural genomics. Countless derived databases and projects have been developed to integrate and classify the PDB in terms of protein structure, protein function and protein evolution. GrowthWhen the PDB was originally founded it contained just 7 protein structures. Since then it has undergone an approximate exponential growth in the number of structures, which does not show any sign of falling off. The growth rate of the PDB has been the subject of fairly extensive analysis. ContentsAs of 26 September, 2006, the database contained 39,051 released atomic coordinate entries (or "structures"), 35,767 of that proteins, the rest being nucleic acids, nucleic acid-protein complexes, and a few other molecules. About 5,000 new structures are released each year. Data are stored in the mmCIF format specifically developed for the purpose. Note that the database stores information about the exact location of all atoms in a large biomolecule (although, usually without the hydrogen atoms, as their positions are more of a statistical estimate); if one is only interested in sequence data, i.e. the list of amino acids making up a particular protein or the list of nucleotides making up a particular nucleic acid, the much larger databases from Swiss-Prot and the International Nucleotide Sequence Database Collaboration should be used. StatisticsAs of 11 September, 2007, the "PDB Holdings List" at RCSB reported the following statistics:
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| Identifiers | ||||||||||||||||||||||||||||||||||||||
| Symbol(s) | MBL2; COLEC1; HSMBPC; MBL; MBP; MBP1; MGC116832; MGC116833 | |||||||||||||||||||||||||||||||||||||
| External IDs | OMIM: 154545 MGI: 96924 Homologene: 88328 | |||||||||||||||||||||||||||||||||||||
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| RNA expression pattern | ||||||||||||||||||||||||||||||||||||||
| Orthologs | ||||||||||||||||||||||||||||||||||||||
| Human | Mouse | |||||||||||||||||||||||||||||||||||||
| Entrez | 4153 | 17195 | ||||||||||||||||||||||||||||||||||||
| Ensembl | ENSG00000165471 | ENSMUSG00000024863 | ||||||||||||||||||||||||||||||||||||
| Uniprot | P11226 | Q3UEK1 | ||||||||||||||||||||||||||||||||||||
| Refseq | NM_000242 (mRNA) NP_000233 (protein) | NM_010776 (mRNA) NP_034906 (protein) | ||||||||||||||||||||||||||||||||||||
| Location | Chr 10: 54.2 - 54.2 Mb | Chr 19: 30.3 - 30.31 Mb | ||||||||||||||||||||||||||||||||||||
| Pubmed search | [5] | [6] | ||||||||||||||||||||||||||||||||||||
Mannose binding lectin (MBL), also named mannose- or mannan-binding protein (MBP), is an important factor in innate immunity.
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.
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 (specifically Mannose and Fucose residues) found on the surface of many pathogens.
For example, MBL has been show to bind to:
- yeasts such as Candida albicans
- viruses such as HIV and influenza A
- many bacteria including Salmonella and Streptococci
- parasites like Leishmania
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.
External links
References
Further reading
- Sheriff, S., Chang, C.Y., Ezekowitz, R.A. (1994) Human mannose-binding protein carbohydrate recognition domain trimerizes through a triple alpha-helical coiled-coil. Nat.Struct.Biol. 1: 789-794
- 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.
- Ji X, Gewurz H, Spear GT (2005). "Mannose binding lectin (MBL) and HIV.". Mol. Immunol. 42 (2): 145-52. doi:10.1016/j.molimm.2004.06.015. PMID 15488604.
- 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.
- Worthley DL, Bardy PG, Gordon DL, Mullighan CG (2007). "Mannose-binding lectin and maladies of the bowel and liver.". World J. Gastroenterol. 12 (40): 6420-8. PMID 17072973.
Proteins: complement system (C, L, A) | |
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| Activators | CLA: C3-convertase - MAC (C6, C7, C8, C9) - L: Mannan-binding lectin - A: Factor P/Properdin |
| Enzymes | C: C1Q/C1R/C1S - C4 - C2 - CLA: C3 - C5 (C5a) - L: MASP1 - MASP2 - A: Factor B - Factor D |
| Inhibitors | CLA: C1-inhibitor - Decay accelerating factor - Factor I - CL: C4BP - A: Factor H |
| Complement receptors | CR1 - CR2 - CR3 - CR4 - CD11b/CD11c/CD18 - Anaphylatoxin (C3a, C5a) |
Acknowledgement and Attribution Regarding Sources of Content
Some of the initial content on this page may be incorporated in part from copyleft sources in the public domain including wikis such as Wikipedia and AskDrWiki. Drug information for patients came from the The National Library of Medicine. Infectious disease information may have come from the Centers for Disease Control (CDC). Differential Diagnoses are drawn from clinicians as well as an amalgamation of 3 sources: 1.The Disease Database; 2. Kahan, Scott, Smith, Ellen G. In A Page: Signs and Symptoms. Malden, Massachusetts: Blackwell Publishing, 2004:3; 3. Sailer, Christian, Wasner, Susanne. Differential Diagnosis Pocket. Hermosa Beach, CA: Borm Bruckmeir Publishing LLC, 2002:7 .
