View source for 8oxx


==Transglutaminase 3 in complex with inhibitor Z-don and DH patient-derived Fab DH63-B02==
<StructureSection load='8oxx' size='340' side='right'caption='[[8oxx]], [[Resolution|resolution]] 2.50&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8oxx]] is a 3 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=8OXX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8OXX FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.5&#8491;</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=DPR:D-PROLINE'>DPR</scene>, <scene name='pdbligand=DVA:D-VALINE'>DVA</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=MLL:METHYL+L-LEUCINATE'>MLL</scene>, <scene name='pdbligand=ONL:5-OXO-L-NORLEUCINE'>ONL</scene>, <scene name='pdbligand=P6S:benzyl+hydrogen+carbonate'>P6S</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=8oxx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8oxx OCA], [https://pdbe.org/8oxx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8oxx RCSB], [https://www.ebi.ac.uk/pdbsum/8oxx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8oxx ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/TGM3_HUMAN TGM3_HUMAN] Catalyzes the calcium-dependent formation of isopeptide cross-links between glutamine and lysine residues in various proteins, as well as the conjugation of polyamines to proteins. Involved in the formation of the cornified envelope (CE), a specialized component consisting of covalent cross-links of proteins beneath the plasma membrane of terminally differentiated keratinocytes. Catalyzes small proline-rich proteins (SPRR1 and SPRR2) and LOR cross-linking to form small interchain oligomers, which are further cross-linked by TGM1 onto the growing CE scaffold (By similarity). In hair follicles, involved in cross-linking structural proteins to hardening the inner root sheath.
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== Publication Abstract from PubMed ==
Transglutaminase 3 (TG3), the autoantigen of dermatitis herpetiformis (DH), is a calcium dependent enzyme that targets glutamine residues in polypeptides for either transamidation or deamidation modifications. To become catalytically active TG3 requires proteolytic cleavage between the core domain and two C-terminal beta-barrels (C1C2). Here, we report four X-ray crystal structures representing inactive and active conformations of human TG3 in complex with a TG3-specific Fab fragment of a DH patient derived antibody. We demonstrate that cleaved TG3, upon binding of a substrate-mimicking inhibitor, undergoes a large conformational change as a beta-sheet in the catalytic core domain moves and C1C2 detaches. The unique enzyme-substrate conformation of TG3 without C1C2 is recognized by DH autoantibodies. The findings support a model where B-cell receptors of TG3-specific B cells bind and internalize TG3-gluten enzyme-substrate complexes thereby facilitating gluten-antigen presentation, T-cell help and autoantibody production.

Autoantibody binding and unique enzyme-substrate intermediate conformation of human transglutaminase 3.,Heggelund JE, Das S, Stamnaes J, Iversen R, Sollid LM Nat Commun. 2023 Oct 5;14(1):6216. doi: 10.1038/s41467-023-42004-z. PMID:37798283<ref>PMID:37798283</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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== References ==
<references/>
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Heggelund JE]]
[[Category: Sollid LM]]