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4aqb

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Revision as of 09:03, 6 March 2019

MBL-Ficolin Associated Protein-1, MAP-1 aka MAP44

Structural highlights

4aqb is a 1 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, , ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[MASP1_HUMAN] Defects in MASP1 are the cause of 3MC syndrome type 1 (3MC1) [MIM:257920]. 3MC1 is a disorder characterized by facial dysmorphism that includes hypertelorism, blepharophimosis, blepharoptosis and highly arched eyebrows, cleft lip and/or palate, craniosynostosis, learning disability and genital, limb and vesicorenal anomalies. The term 3MC syndrome includes Carnevale, Mingarelli, Malpuech, and Michels syndromes.^[1]

Function

[MASP1_HUMAN] 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.^[2] ^[3]

Publication Abstract from PubMed

The human lectin complement pathway activation molecules comprise mannose-binding lectin (MBL) and ficolin-1, -2, and -3 in complex with associated serine proteases MASP-1, -2, and -3 and the non-enzymatic small MBL associated protein or sMAP. Recently, a novel plasma protein named MBL/ficolin-associated protein-1 (MAP-1) was identified in humans. This protein is the result of a differential splicing of the MASP1 gene and includes the major part of the heavy chain but lacks the serine protease domain. We investigated the direct interactions of MAP-1 and MASP-3 with ficolin-3 and MBL using surface plasmon resonance and found affinities around 5 nm and 2.5 nm, respectively. We studied structural aspects of MAP-1 and could show by multi-angle laser light scattering that MAP-1 forms a calcium-dependent homodimer in solution. We were able to determine the crystal structure of MAP-1, which also contains a head-to-tail dimer approximately 146 A long. This structure of MAP-1 also enables modeling and assembly of the MASP-1 molecule in its entirety. Finally we found that MAP-1 competes with all three MASPs for ligand binding and is able to mediate a strong dose-dependent inhibitory effect on the lectin pathway activation, as measured by levels of C3 and C9.

Crystal Structure and Functional Characterization of the Complement Regulator Mannose-binding Lectin (MBL)/Ficolin-associated Protein-1 (MAP-1).,Skjoedt MO, Roversi P, Hummelshoj T, Palarasah Y, Rosbjerg A, Johnson S, Lea SM, Garred P J Biol Chem. 2012 Sep 21;287(39):32913-21. Epub 2012 Aug 1. PMID:22854970^[4]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Rooryck C, Diaz-Font A, Osborn DP, Chabchoub E, Hernandez-Hernandez V, Shamseldin H, Kenny J, Waters A, Jenkins D, Kaissi AA, Leal GF, Dallapiccola B, Carnevale F, Bitner-Glindzicz M, Lees M, Hennekam R, Stanier P, Burns AJ, Peeters H, Alkuraya FS, Beales PL. Mutations in lectin complement pathway genes COLEC11 and MASP1 cause 3MC syndrome. Nat Genet. 2011 Mar;43(3):197-203. doi: 10.1038/ng.757. Epub 2011 Jan 23. PMID:21258343 doi:10.1038/ng.757
↑ Dahl MR, Thiel S, Matsushita M, Fujita T, Willis AC, Christensen T, Vorup-Jensen T, Jensenius JC. MASP-3 and its association with distinct complexes of the mannan-binding lectin complement activation pathway. Immunity. 2001 Jul;15(1):127-35. PMID:11485744
↑ Moller-Kristensen M, Thiel S, Sjoholm A, Matsushita M, Jensenius JC. Cooperation between MASP-1 and MASP-2 in the generation of C3 convertase through the MBL pathway. Int Immunol. 2007 Feb;19(2):141-9. Epub 2006 Dec 20. PMID:17182967 doi:dxl131
↑ Skjoedt MO, Roversi P, Hummelshoj T, Palarasah Y, Rosbjerg A, Johnson S, Lea SM, Garred P. Crystal Structure and Functional Characterization of the Complement Regulator Mannose-binding Lectin (MBL)/Ficolin-associated Protein-1 (MAP-1). J Biol Chem. 2012 Sep 21;287(39):32913-21. Epub 2012 Aug 1. PMID:22854970 doi:http://dx.doi.org/10.1074/jbc.M112.386680

1 Structural highlights
2 Disease
3 Function
4 Publication Abstract from PubMed
5 See Also
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4aqb"

@@ Line 1: / Line 1: @@
 ==MBL-Ficolin Associated Protein-1, MAP-1 aka MAP44==
-<StructureSection load='4aqb' size='340' side='right' caption='[[4aqb]], [[Resolution|resolution]] 4.20&Aring;' scene=''>
+<StructureSection load='4aqb' size='340' side='right'caption='[[4aqb]], [[Resolution|resolution]] 4.20&Aring;' scene=''>
 == Structural highlights ==
 <table><tr><td colspan='2'>[[4aqb]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4AQB OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4AQB FirstGlance]. <br>
@@ Line 20: / Line 20: @@
 </div>
 <div class="pdbe-citations 4aqb" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Mannan-binding lectin serine protease|Mannan-binding lectin serine protease]]
 == References ==
 <references/>

4aqb

From Proteopedia

Revision as of 09:03, 6 March 2019

MBL-Ficolin Associated Protein-1, MAP-1 aka MAP44

Structural highlights

Disease

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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