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1nzi

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[[Image:1nzi.jpg|left|200px]]<br /><applet load="1nzi" size="350" color="white" frame="true" align="right" spinBox="true"
 
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caption="1nzi, resolution 1.5&Aring;" />
 
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'''Crystal Structure of the CUB1-EGF Interaction Domain of Complement Protease C1s'''<br />
 
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==Overview==
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==Crystal Structure of the CUB1-EGF Interaction Domain of Complement Protease C1s==
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C1, the complex that triggers the classical pathway of complement, is, assembled from two modular proteases C1r and C1s and a recognition protein, C1q. The N-terminal CUB1-EGF segments of C1r and C1s are key elements of, the C1 architecture, because they mediate both Ca2+-dependent C1r-C1s, association and interaction with C1q. The crystal structure of the, interaction domain of C1s has been solved and refined to 1.5 A resolution., The structure reveals a head-to-tail homodimer involving interactions, between the CUB1 module of one monomer and the epidermal growth factor, (EGF) module of its counterpart. A Ca2+ ion is bound to each EGF module, and stabilizes both the intra- and inter-monomer interfaces. Unexpectedly, a second Ca2+ ion is bound to the distal end of each CUB1 module, through, six ligands contributed by Glu45, Asp53, Asp98, and two water molecules., These acidic residues and Tyr17 are conserved in approximately two-thirds, of the CUB repertoire and define a novel, Ca2+-binding CUB module subset., The C1s structure was used to build a model of the C1r-C1s CUB1-EGF, heterodimer, which in C1 connects C1r to C1s and mediates interaction with, C1q. A structural model of the C1q/C1r/C1s interface is proposed, where, the rod-like collagen triple helix of C1q is accommodated into a groove, along the transversal axis of the C1r-C1s heterodimer.
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<StructureSection load='1nzi' size='340' side='right'caption='[[1nzi]], [[Resolution|resolution]] 1.50&Aring;' scene=''>
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== Structural highlights ==
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==Disease==
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<table><tr><td colspan='2'>[[1nzi]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1NZI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1NZI FirstGlance]. <br>
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Known diseases associated with this structure: C1r/C1s deficiency, combined OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=120580 120580]], C1s deficiency, isolated OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=120580 120580]]
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.5&#8491;</td></tr>
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<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=MG:MAGNESIUM+ION'>MG</scene></td></tr>
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==About this Structure==
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1nzi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1nzi OCA], [https://pdbe.org/1nzi PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1nzi RCSB], [https://www.ebi.ac.uk/pdbsum/1nzi PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1nzi ProSAT]</span></td></tr>
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1NZI is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=CA:'>CA</scene> and <scene name='pdbligand=MG:'>MG</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Complement_subcomponent_C1s Complement subcomponent C1s], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.42 3.4.21.42] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1NZI OCA].
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</table>
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== Disease ==
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==Reference==
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[https://www.uniprot.org/uniprot/C1S_HUMAN C1S_HUMAN] Defects in C1S are the cause of complement component C1s deficiency (C1SD) [MIM:[https://omim.org/entry/613783 613783]. A rare defect resulting in C1 deficiency and impaired activation of the complement classical pathway. C1 deficiency generally leads to severe immune complex disease with features of systemic lupus erythematosus and glomerulonephritis.
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X-ray structure of the Ca2+-binding interaction domain of C1s. Insights into the assembly of the C1 complex of complement., Gregory LA, Thielens NM, Arlaud GJ, Fontecilla-Camps JC, Gaboriaud C, J Biol Chem. 2003 Aug 22;278(34):32157-64. Epub 2003 Jun 4. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=12788922 12788922]
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== Function ==
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[[Category: Complement subcomponent C1s]]
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[https://www.uniprot.org/uniprot/C1S_HUMAN C1S_HUMAN] C1s B chain is a serine protease that combines with C1q and C1r to form C1, the first component of the classical pathway of the complement system. C1r activates C1s so that it can, in turn, activate C2 and C4.
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/nz/1nzi_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1nzi ConSurf].
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<div style="clear:both"></div>
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__TOC__
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Single protein]]
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[[Category: Large Structures]]
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[[Category: Arlaud, G.J.]]
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[[Category: Arlaud GJ]]
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[[Category: Fontecilla-Camps, J.C.]]
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[[Category: Fontecilla-Camps JC]]
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[[Category: Gaboriaud, C.]]
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[[Category: Gaboriaud C]]
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[[Category: Gregory, L.A.]]
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[[Category: Gregory LA]]
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[[Category: Thielens, N.M.]]
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[[Category: Thielens NM]]
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[[Category: CA]]
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[[Category: MG]]
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[[Category: calcium]]
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[[Category: complement]]
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[[Category: cub]]
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[[Category: egf]]
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[[Category: innate immunity]]
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[[Category: modular structure]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri Feb 15 16:31:32 2008''
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Current revision

Crystal Structure of the CUB1-EGF Interaction Domain of Complement Protease C1s

PDB ID 1nzi

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