1hzf

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[[Image:1hzf.png|left|200px]]
 
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{{STRUCTURE_1hzf| PDB=1hzf | SCENE= }}
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==C4ADG FRAGMENT OF HUMAN COMPLEMENT FACTOR C4A==
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<StructureSection load='1hzf' size='340' side='right'caption='[[1hzf]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[1hzf]] is a 1 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=1HZF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1HZF FirstGlance]. <br>
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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]] 2.3&#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=MSE:SELENOMETHIONINE'>MSE</scene></td></tr>
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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=1hzf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1hzf OCA], [https://pdbe.org/1hzf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1hzf RCSB], [https://www.ebi.ac.uk/pdbsum/1hzf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1hzf ProSAT]</span></td></tr>
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</table>
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== Disease ==
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[https://www.uniprot.org/uniprot/CO4A_HUMAN CO4A_HUMAN] Defects in C4A are the cause of complement component 4A deficiency (C4AD) [MIM:[https://omim.org/entry/614380 614380]. A rare defect of the complement classical pathway associated with the development of autoimmune disorders, mainly systemic lupus with or without associated glomerulonephritis.<ref>PMID:8473511</ref> Defects in C4A are a cause of susceptibility to systemic lupus erythematosus (SLE) [MIM:[https://omim.org/entry/152700 152700]. A chronic, inflammatory and often febrile multisystemic disorder of connective tissue. It affects principally the skin, joints, kidneys and serosal membranes. It is thought to represent a failure of the regulatory mechanisms of the autoimmune system. Note=Interindividual copy-number variation (CNV) of complement component C4 and associated polymorphisms result in different susceptibilities to SLE. The risk of SLE susceptibility has been shown to be significantly increased among subjects with only two copies of total C4. A high copy number is a protective factor against SLE.<ref>PMID:17503323</ref>
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== Function ==
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[https://www.uniprot.org/uniprot/CO4A_HUMAN CO4A_HUMAN] C4 plays a central role in the activation of the classical pathway of the complement system. It is processed by activated C1 which removes from the alpha chain the C4a anaphylatoxin. The remaining alpha chain fragment C4b is the major activation product and is an essential subunit of the C3 convertase (C4b2a) and the C5 convertase (C3bC4b2a) enzymes of the classical complement pathway. Derived from proteolytic degradation of complement C4, C4a anaphylatoxin is a mediator of local inflammatory process. It induces the contraction of smooth muscle, increases vascular permeability and causes histamine release from mast cells and basophilic leukocytes.
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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/hz/1hzf_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.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=1hzf ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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C4 fulfills a vital role in the propagation of the classical and lectin pathways of the complement system. Although there are no reports to date of a C4 functional activity that is mediated solely by the C4d region, evidence clearly points to it having a vital role in a number of the properties of native C4 and its major activation fragment, C4b. Contained within the C4d region are the thioester-forming residues, the four isotype-specific residues controlling the C4A/C4B transacylation preferences, a binding site for nascent C3b important in assembling the classical pathway C5 convertase and determinants for the Chido/Rodgers (Ch/Rg) blood group antigens. In view of its functional importance, we undertook to determine the three-dimensional structure of C4d by X-ray crystallography. Here we report the 2.3A resolution structure of C4Ad, the C4d fragment derived from the human C4A isotype. Although the approximately 30% sequence identity between C4Ad and the corresponding fragment of C3 might be expected to establish a general fold similarity between the two molecules, C4Ad in fact displays a fold that is essentially superimposable on the structure of C3d. By contrast, the electrostatic characteristics of the various faces of the C4Ad molecule show marked differences from the corresponding faces of C3d, likely reflecting the differences in function between C3 and C4. Residues previously predicted to form the major Ch/Rg epitopes were proximately located and accessible on the concave surface of C4Ad. In addition to providing further insights on the current models for the covalent binding reaction, the C4Ad structure allows one to rationalize why C4d is not a ligand for complement receptor 2. Finally the structure allows for the visualization of the face of the molecule containing the binding site for C3b utilized in the assembly of classical pathway C5 convertase.
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===C4ADG FRAGMENT OF HUMAN COMPLEMENT FACTOR C4A===
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X-ray crystal structure of the C4d fragment of human complement component C4.,van den Elsen JM, Martin A, Wong V, Clemenza L, Rose DR, Isenman DE J Mol Biol. 2002 Oct 4;322(5):1103-15. PMID:12367531<ref>PMID:12367531</ref>
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{{ABSTRACT_PUBMED_12367531}}
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 1hzf" style="background-color:#fffaf0;"></div>
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==About this Structure==
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==See Also==
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[[1hzf]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1HZF OCA].
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*[[Complement C4|Complement C4]]
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== References ==
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==Reference==
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<references/>
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<ref group="xtra">PMID:012367531</ref><references group="xtra"/>
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__TOC__
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[[Category: Classical-complement-pathway C3/C5 convertase]]
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Clemenza, L.]]
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[[Category: Large Structures]]
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[[Category: Elsen, J M.H van den.]]
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[[Category: Clemenza L]]
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[[Category: Isenman, D E.]]
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[[Category: Isenman DE]]
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[[Category: Martin, A.]]
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[[Category: Martin A]]
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[[Category: Rose, D R.]]
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[[Category: Rose DR]]
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[[Category: Wong, V.]]
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[[Category: Wong V]]
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[[Category: Alpha-alpha 6 barrel]]
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[[Category: Van den Elsen JMH]]
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[[Category: Immune system]]
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Current revision

C4ADG FRAGMENT OF HUMAN COMPLEMENT FACTOR C4A

PDB ID 1hzf

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