6w9g

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==Crystal Structure of the Fab fragment of humanized 5c8 antibody containing the fluorescent non-canonical amino acid L-(7-hydroxycoumarin-4-yl)ethylglycine in complex with CD40L at pH 6.8==
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<StructureSection load='6w9g' size='340' side='right'caption='[[6w9g]]' scene=''>
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<StructureSection load='6w9g' size='340' side='right'caption='[[6w9g]], [[Resolution|resolution]] 1.82&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id= OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol= FirstGlance]. <br>
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<table><tr><td colspan='2'>[[6w9g]] is a 9 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=6W9G OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6W9G FirstGlance]. <br>
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</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6w9g FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6w9g OCA], [http://pdbe.org/6w9g PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6w9g RCSB], [http://www.ebi.ac.uk/pdbsum/6w9g PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6w9g ProSAT]</span></td></tr>
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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]] 1.82&#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=1PE:PENTAETHYLENE+GLYCOL'>1PE</scene>, <scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=DV7:L-(7-hydroxycoumarin-4-yl)ethylglycine'>DV7</scene>, <scene name='pdbligand=ETE:2-{2-[2-2-(METHOXY-ETHOXY)-ETHOXY]-ETHOXY}-ETHANOL'>ETE</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=TMO:TRIMETHYLAMINE+OXIDE'>TMO</scene>, <scene name='pdbligand=TRS:2-AMINO-2-HYDROXYMETHYL-PROPANE-1,3-DIOL'>TRS</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=6w9g FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6w9g OCA], [https://pdbe.org/6w9g PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6w9g RCSB], [https://www.ebi.ac.uk/pdbsum/6w9g PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6w9g ProSAT]</span></td></tr>
</table>
</table>
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== Disease ==
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[https://www.uniprot.org/uniprot/CD40L_HUMAN CD40L_HUMAN] Defects in CD40LG are the cause of X-linked immunodeficiency with hyper-IgM type 1 (HIGM1) [MIM:[https://omim.org/entry/308230 308230]; also known as X-linked hyper IgM syndrome (XHIM). HIGM1 is an immunoglobulin isotype switch defect characterized by elevated concentrations of serum IgM and decreased amounts of all other isotypes. Affected males present at an early age (usually within the first year of life) recurrent bacterial and opportunistic infections, including Pneumocystis carinii pneumonia and intractable diarrhea due to cryptosporidium infection. Despite substitution treatment with intravenous immunoglobulin, the overall prognosis is rather poor, with a death rate of about 10% before adolescence.<ref>PMID:7678782</ref> <ref>PMID:7679206</ref> <ref>PMID:8094231</ref> <ref>PMID:7679801</ref> <ref>PMID:7717401</ref> <ref>PMID:7532185</ref> <ref>PMID:8889581</ref> <ref>PMID:8550833</ref> <ref>PMID:9150729</ref> <ref>PMID:9746782</ref>
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== Function ==
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[https://www.uniprot.org/uniprot/CD40L_HUMAN CD40L_HUMAN] Mediates B-cell proliferation in the absence of co-stimulus as well as IgE production in the presence of IL-4. Involved in immunoglobulin class switching.<ref>PMID:15193700</ref> Release of soluble CD40L from platelets is partially regulated by GP IIb/IIIa, actin polymerization, and an matrix metalloproteinases (MMP) inhibitor-sensitive pathway.<ref>PMID:15193700</ref>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Genetically encoded fluorescent noncanonical amino acids (fNCAAs) could be used to develop novel fluorescent sensors of protein function. Previous efforts toward this goal have been limited by the lack of extensive physicochemical and structural characterizations of protein-based sensors containing fNCAAs. Here, we report the steady-state spectroscopic properties and first structural analyses of an fNCAA-containing Fab fragment of the 5c8 antibody, which binds human CD40L. A previously reported 5c8 variant in which the light chain residue Ile(L)98 is replaced with the fNCAA l-(7-hydroxycoumarin-4-yl)ethylglycine (7-HCAA) exhibits a 1.7-fold increase in fluorescence upon antigen binding. Determination and comparison of the apparent pKas of 7-HCAA in the unbound and bound forms indicate that the observed increase in fluorescence is not the result of perturbations in pKa. Crystal structures of the fNCAA-containing Fab in the apo and bound forms reveal interactions between the 7-HCAA side chain and surrounding residues that are disrupted upon antigen binding. This structural characterization not only provides insight into the manner in which protein environments can modulate the fluorescence properties of 7-HCAA but also could serve as a starting point for the rational design of new fluorescent protein-based reporters of protein function.
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Structural Insights into How Protein Environments Tune the Spectroscopic Properties of a Noncanonical Amino Acid Fluorophore.,Henderson JN, Simmons CR, Fahmi NE, Jeffs JW, Borges CR, Mills JH Biochemistry. 2020 Sep 22;59(37):3401-3410. doi: 10.1021/acs.biochem.0c00474., Epub 2020 Sep 3. PMID:32845612<ref>PMID:32845612</ref>
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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 6w9g" style="background-color:#fffaf0;"></div>
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==See Also==
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*[[Antibody 3D structures|Antibody 3D structures]]
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*[[Tumor necrosis factor receptor 3D structures|Tumor necrosis factor receptor 3D structures]]
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== References ==
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<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
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[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Large Structures]]
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[[Category: Z-disk]]
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[[Category: Henderson JN]]
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[[Category: Mills JH]]
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[[Category: Simmons CR]]

Revision as of 14:19, 18 October 2023

Crystal Structure of the Fab fragment of humanized 5c8 antibody containing the fluorescent non-canonical amino acid L-(7-hydroxycoumarin-4-yl)ethylglycine in complex with CD40L at pH 6.8

PDB ID 6w9g

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