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| | ==Crystal structure of MASP-1 CUB2 domain bound to Ethylamine== | | ==Crystal structure of MASP-1 CUB2 domain bound to Ethylamine== |
| - | <StructureSection load='3poj' size='340' side='right' caption='[[3poj]], [[Resolution|resolution]] 1.45Å' scene=''> | + | <StructureSection load='3poj' size='340' side='right'caption='[[3poj]], [[Resolution|resolution]] 1.45Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3poj]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Buffalo_rat Buffalo rat]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3POJ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3POJ FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3poj]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3POJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3POJ FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=NEH:ETHANAMINE'>NEH</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=TRS:2-AMINO-2-HYDROXYMETHYL-PROPANE-1,3-DIOL'>TRS</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.451Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3pob|3pob]], [[3pof|3pof]]</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=NEH:ETHANAMINE'>NEH</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=TRS:2-AMINO-2-HYDROXYMETHYL-PROPANE-1,3-DIOL'>TRS</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Crarf, MASP-1/-3, Masp1, Masp3 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10116 Buffalo rat])</td></tr>
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3poj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3poj OCA], [https://pdbe.org/3poj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3poj RCSB], [https://www.ebi.ac.uk/pdbsum/3poj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3poj ProSAT]</span></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3poj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3poj OCA], [http://pdbe.org/3poj PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3poj RCSB], [http://www.ebi.ac.uk/pdbsum/3poj PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3poj ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/MASP1_RAT MASP1_RAT]] Functions in the lectin pathway of complement, which performs a key role in innate immunity by recognizing pathogens through patterns of sugar moieties and neutralizing them. The lectin pathway is triggered upon binding of mannan-binding lectin (MBL) and ficolins to sugar moieties which leads to activation of the associated proteases MASP1 and MASP2. Functions as an endopeptidase and may activate MASP2 or C2 or directly activate C3 the key component of complement reaction. Isoform 2 may have an inhibitory effect on the activation of the lectin pathway of complement or may cleave IGFBP5 (By similarity). | + | [https://www.uniprot.org/uniprot/MASP1_RAT MASP1_RAT] Functions in the lectin pathway of complement, which performs a key role in innate immunity by recognizing pathogens through patterns of sugar moieties and neutralizing them. The lectin pathway is triggered upon binding of mannan-binding lectin (MBL) and ficolins to sugar moieties which leads to activation of the associated proteases MASP1 and MASP2. Functions as an endopeptidase and may activate MASP2 or C2 or directly activate C3 the key component of complement reaction. Isoform 2 may have an inhibitory effect on the activation of the lectin pathway of complement or may cleave IGFBP5 (By similarity). |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </div> | | </div> |
| | <div class="pdbe-citations 3poj" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 3poj" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Mannan-binding lectin serine protease|Mannan-binding lectin serine protease]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Buffalo rat]] | + | [[Category: Large Structures]] |
| - | [[Category: Gingras, A R]] | + | [[Category: Rattus norvegicus]] |
| - | [[Category: Moody, P C.E]] | + | [[Category: Gingras AR]] |
| - | [[Category: Wallis, R]] | + | [[Category: Moody PCE]] |
| - | [[Category: Bloodstream]] | + | [[Category: Wallis R]] |
| - | [[Category: Ca2+ binding site]]
| + | |
| - | [[Category: Complement protein]]
| + | |
| - | [[Category: Complex with ethylamine]]
| + | |
| - | [[Category: Cub domain]]
| + | |
| - | [[Category: Ficolin]]
| + | |
| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: Lectin pathway of complement]]
| + | |
| - | [[Category: Mbl]]
| + | |
| - | [[Category: Mbp]]
| + | |
| Structural highlights
Function
MASP1_RAT Functions in the lectin pathway of complement, which performs a key role in innate immunity by recognizing pathogens through patterns of sugar moieties and neutralizing them. The lectin pathway is triggered upon binding of mannan-binding lectin (MBL) and ficolins to sugar moieties which leads to activation of the associated proteases MASP1 and MASP2. Functions as an endopeptidase and may activate MASP2 or C2 or directly activate C3 the key component of complement reaction. Isoform 2 may have an inhibitory effect on the activation of the lectin pathway of complement or may cleave IGFBP5 (By similarity).
Publication Abstract from PubMed
Complement activation contributes directly to health and disease. It neutralizes pathogens and stimulates immune processes. Defects lead to immunodeficiency and autoimmune diseases, whereas inappropriate activation causes self-damage. In the lectin and classical pathways, complement is triggered upon recognition of a pathogen by an activating complex. Here we present the first structure of such a complex in the form of the collagen-like domain of mannan-binding lectin (MBL) and the binding domain of its associated protease (MASP-1/-3). The collagen binds within a groove using a pivotal lysine side chain that interacts with Ca(2+)-coordinating residues, revealing the essential role of Ca(2+). This mode of binding is prototypic for all activating complexes of the lectin and classical pathways, and suggests a general mechanism for the global changes that drive activation. The structural insights reveal a new focus for inhibitors and we have validated this concept by targeting the binding pocket of the MASP.
Structural Basis of Mannan-Binding Lectin Recognition by Its Associated Serine Protease MASP-1: Implications for Complement Activation.,Gingras AR, Girija UV, Keeble AH, Panchal R, Mitchell DA, Moody PC, Wallis R Structure. 2011 Nov 9;19(11):1635-43. PMID:22078562[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Gingras AR, Girija UV, Keeble AH, Panchal R, Mitchell DA, Moody PC, Wallis R. Structural Basis of Mannan-Binding Lectin Recognition by Its Associated Serine Protease MASP-1: Implications for Complement Activation. Structure. 2011 Nov 9;19(11):1635-43. PMID:22078562 doi:10.1016/j.str.2011.08.014
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