View source for 8c67


==Crystal structure of Ab25 Fab==
<StructureSection load='8c67' size='340' side='right'caption='[[8c67]], [[Resolution|resolution]] 1.88&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8c67]] is a 8 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=8C67 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8C67 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]] 1.88&#8491;</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=8c67 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8c67 OCA], [https://pdbe.org/8c67 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8c67 RCSB], [https://www.ebi.ac.uk/pdbsum/8c67 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8c67 ProSAT]</span></td></tr>
</table>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Streptococcus pyogenes can cause invasive disease with high mortality despite adequate antibiotic treatments. To address this unmet need, we have previously generated an opsonic IgG1 monoclonal antibody, Ab25, targeting the bacterial M protein. Here, we engineer the IgG2-4 subclasses of Ab25. Despite having reduced binding, the IgG3 version promotes stronger phagocytosis of bacteria. Using atomic simulations, we show that IgG3's Fc tail has extensive movement in 3D space due to its extended hinge region, possibly facilitating interactions with immune cells. We replaced the hinge of IgG1 with four different IgG3-hinge segment subclasses, IgGh(xx). Hinge-engineering does not diminish binding as with IgG3 but enhances opsonic function, where a 47 amino acid hinge is comparable to IgG3 in function. IgGh(47) shows improved protection against S. pyogenes in a systemic infection mouse model, suggesting that IgGh(47) has promise as a preclinical therapeutic candidate. Importantly, the enhanced opsonic function of IgGh(47) is generalizable to diverse S. pyogenes strains from clinical isolates. We generated IgGh(47) versions of anti-SARS-CoV-2 mAbs to broaden the biological applicability, and these also exhibit strongly enhanced opsonic function compared to the IgG1 subclass. The improved function of the IgGh(47) subclass in two distant biological systems provides new insights into antibody function.

The hinge-engineered IgG1-IgG3 hybrid subclass IgGh(47) potently enhances Fc-mediated function of anti-streptococcal and SARS-CoV-2 antibodies.,Izadi A, Karami Y, Bratanis E, Wrighton S, Khakzad H, Nyblom M, Olofsson B, Happonen L, Tang D, Sundwall M, Godzwon M, Chao Y, Toledo AG, Schmidt T, Ohlin M, Nilges M, Malmstrom J, Bahnan W, Shannon O, Malmstrom L, Nordenfelt P Nat Commun. 2024 Apr 27;15(1):3600. doi: 10.1038/s41467-024-47928-8. PMID:38678029<ref>PMID:38678029</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 8c67" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Bahnan W]]
[[Category: Happonen L]]
[[Category: Izadi A]]
[[Category: Malmstroem J]]
[[Category: Malmstroem L]]
[[Category: Nordenfelt P]]
[[Category: Nyblom M]]
[[Category: Shannon O]]
[[Category: Tang D]]