6i1o
From Proteopedia
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<StructureSection load='6i1o' size='340' side='right'caption='[[6i1o]], [[Resolution|resolution]] 1.93Å' scene=''> | <StructureSection load='6i1o' size='340' side='right'caption='[[6i1o]], [[Resolution|resolution]] 1.93Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
- | <table><tr><td colspan='2'>[[6i1o]] is a 2 chain structure with sequence from [ | + | <table><tr><td colspan='2'>[[6i1o]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6I1O OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6I1O FirstGlance]. <br> |
- | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BTB:2-[BIS-(2-HYDROXY-ETHYL)-AMINO]-2-HYDROXYMETHYL-PROPANE-1,3-DIOL'>BTB</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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]] 1.93Å</td></tr> |
- | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BTB:2-[BIS-(2-HYDROXY-ETHYL)-AMINO]-2-HYDROXYMETHYL-PROPANE-1,3-DIOL'>BTB</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></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=6i1o FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6i1o OCA], [https://pdbe.org/6i1o PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6i1o RCSB], [https://www.ebi.ac.uk/pdbsum/6i1o PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6i1o ProSAT]</span></td></tr> | ||
</table> | </table> | ||
+ | <div style="background-color:#fffaf0;"> | ||
+ | == Publication Abstract from PubMed == | ||
+ | The alpha-1-antitrypsin (or alpha-1-antitrypsin, A1AT) Z variant is the primary cause of severe A1AT deficiency and forms polymeric chains that aggregate in the endoplasmic reticulum of hepatocytes. Around 2%-5% of Europeans are heterozygous for the Z and WT M allele, and there is evidence of increased risk of liver disease when compared with MM A1AT individuals. We have shown that Z and M A1AT can copolymerize in cell models, but there has been no direct observation of heteropolymer formation in vivo. To this end, we developed a monoclonal antibody (mAb2H2) that specifically binds to M in preference to Z A1AT, localized its epitope using crystallography to a region perturbed by the Z (Glu342Lys) substitution, and used Fab fragments to label polymers isolated from an MZ heterozygote liver explant. Glu342 is critical to the affinity of mAb2H2, since it also recognized the mild S-deficiency variant (Glu264Val) present in circulating polymers from SZ heterozygotes. Negative-stain electron microscopy of the Fab2H2-labeled liver polymers revealed that M comprises around 6% of the polymer subunits in the MZ liver sample. These data demonstrate that Z A1AT can form heteropolymers with polymerization-inert variants in vivo with implications for liver disease in heterozygous individuals. | ||
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+ | Intrahepatic heteropolymerization of M and Z alpha-1-antitrypsin.,Laffranchi M, Elliston EL, Miranda E, Perez J, Ronzoni R, Jagger AM, Heyer-Chauhan N, Brantly ML, Fra A, Lomas DA, Irving JA JCI Insight. 2020 Jul 23;5(14). pii: 135459. doi: 10.1172/jci.insight.135459. PMID:32699193<ref>PMID:32699193</ref> | ||
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+ | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
+ | </div> | ||
+ | <div class="pdbe-citations 6i1o" style="background-color:#fffaf0;"></div> | ||
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+ | ==See Also== | ||
+ | *[[Monoclonal Antibodies 3D structures|Monoclonal Antibodies 3D structures]] | ||
+ | == References == | ||
+ | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Mus musculus]] | [[Category: Mus musculus]] | ||
- | [[Category: Elliston | + | [[Category: Elliston ELK]] |
- | [[Category: Fra | + | [[Category: Fra A]] |
- | [[Category: Irving | + | [[Category: Irving JA]] |
- | [[Category: Laffranchi | + | [[Category: Laffranchi M]] |
- | [[Category: Lomas | + | [[Category: Lomas DA]] |
- | [[Category: Miranda | + | [[Category: Miranda E]] |
- | [[Category: Perez | + | [[Category: Perez J]] |
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Current revision
Fab fragment of an antibody selective for wild-type alpha-1-antitrypsin
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Categories: Large Structures | Mus musculus | Elliston ELK | Fra A | Irving JA | Laffranchi M | Lomas DA | Miranda E | Perez J