7sgm

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Current revision (16:51, 18 October 2023) (edit) (undo)
 
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==Crystal structure of a Fab variant containing a fluorescent noncanonical amino acid with blocked excited state proton transfer and in complex with its antigen, CD40L==
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<StructureSection load='7sgm' size='340' side='right'caption='[[7sgm]]' scene=''>
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<StructureSection load='7sgm' size='340' side='right'caption='[[7sgm]], [[Resolution|resolution]] 2.00&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 [https://proteopedia.org/fgij/fg.htm?mol= FirstGlance]. <br>
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<table><tr><td colspan='2'>[[7sgm]] 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=7SGM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7SGM FirstGlance]. <br>
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</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=7sgm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7sgm OCA], [https://pdbe.org/7sgm PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7sgm RCSB], [https://www.ebi.ac.uk/pdbsum/7sgm PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7sgm 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]] 2&#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=DV7:L-(7-hydroxycoumarin-4-yl)ethylglycine'>DV7</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=7sgm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7sgm OCA], [https://pdbe.org/7sgm PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7sgm RCSB], [https://www.ebi.ac.uk/pdbsum/7sgm PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7sgm 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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The fluorescent non-canonical amino acid (fNCAA) L-(7-hydroxycoumarin-4-yl)ethylglycine (7-HCAA) contains a photoacidic 7-hydroxycoumarin (7-HC) side chain whose fluorescence properties can be tuned by its environment. In proteins, many alterations to 7-HCAA's fluorescence spectra have been reported including increases and decreases in intensity and red- and blue-shifted emission maxima. The ability to rationally design protein environments that alter 7-HCAA's fluorescence properties in predictable ways could lead to novel protein-based sensors of biological function. However, these efforts are likely limited by a lack of structural characterization of 7-HCAA-containing proteins. Here, we report the steady-state spectroscopic and x-ray crystallographic characterization of a 7-HCAA-containing antibody fragment (in the apo and antigen-bound forms) in which a substantially blue-shifted 7-HCAA emission maximum ( approximately 70 nm) is observed relative to the free amino acid. Our structural characterization of these proteins provides evidence that the blue shift is a consequence of the fact that excited state proton transfer (ESPT) from the 7-HC phenol has been almost completely blocked by interactions with the protein backbone. Furthermore, a direct interaction between a residue in the antigen and the fluorophore served to further block proton transfer relative to the apoprotein. The structural basis of the unprecedented blue shift in 7-HCAA emission reported here provides a framework for the development of new fluorescent protein-based sensors.
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Structural Basis for Blocked Excited State Proton Transfer in a Fluorescent, Photoacidic Non-Canonical Amino Acid-Containing Antibody Fragment.,Henderson JN, Simmons CR, Mills JH J Mol Biol. 2022 Apr 30;434(8):167455. doi: 10.1016/j.jmb.2022.167455. Epub 2022 , Jan 13. PMID:35033559<ref>PMID:35033559</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 7sgm" 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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== 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]]

Current revision

Crystal structure of a Fab variant containing a fluorescent noncanonical amino acid with blocked excited state proton transfer and in complex with its antigen, CD40L

PDB ID 7sgm

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