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| | ==Crystal structure of S25-26 in complex with Kdo(2.8)Kdo(2.4)Kdo trisaccharide== | | ==Crystal structure of S25-26 in complex with Kdo(2.8)Kdo(2.4)Kdo trisaccharide== |
| - | <StructureSection load='4m7j' size='340' side='right' caption='[[4m7j]], [[Resolution|resolution]] 1.95Å' scene=''> | + | <StructureSection load='4m7j' size='340' side='right'caption='[[4m7j]], [[Resolution|resolution]] 1.95Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4m7j]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4M7J OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4M7J FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4m7j]] 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=4M7J OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4M7J FirstGlance]. <br> |
| - | </td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=KDA:(3-DEOXY-D-MANNO-OCT-2-ULOSONIC+ACID)-2-O-ALLYL'>KDA</scene>, <scene name='pdbligand=KDO:3-DEOXY-D-MANNO-OCT-2-ULOSONIC+ACID'>KDO</scene><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]] 1.95Å</td></tr> |
| - | <tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4m7z|4m7z]], [[4m93|4m93]], [[4ma1|4ma1]]</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=KDA:(3-DEOXY-D-MANNO-OCT-2-ULOSONIC+ACID)-2-O-ALLYL'>KDA</scene>, <scene name='pdbligand=KDO:3-DEOXY-D-MANNO-OCT-2-ULOSONIC+ACID'>KDO</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene></td></tr> |
| - | <tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4m7j FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4m7j OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4m7j RCSB], [http://www.ebi.ac.uk/pdbsum/4m7j PDBsum]</span></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=4m7j FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4m7j OCA], [https://pdbe.org/4m7j PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4m7j RCSB], [https://www.ebi.ac.uk/pdbsum/4m7j PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4m7j ProSAT]</span></td></tr> |
| - | <table> | + | </table> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| | </div> | | </div> |
| | + | <div class="pdbe-citations 4m7j" style="background-color:#fffaf0;"></div> |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| | + | [[Category: Large Structures]] |
| | [[Category: Mus musculus]] | | [[Category: Mus musculus]] |
| - | [[Category: Brade, H.]] | + | [[Category: Brade H]] |
| - | [[Category: Brade, L.]] | + | [[Category: Brade L]] |
| - | [[Category: Evans, S V.]] | + | [[Category: Evans SV]] |
| - | [[Category: Haji-Ghassemi, O.]] | + | [[Category: Haji-Ghassemi O]] |
| - | [[Category: Harvey, D J.]] | + | [[Category: Harvey DJ]] |
| - | [[Category: Kosma, P.]] | + | [[Category: Kosma P]] |
| - | [[Category: Muller-Loennies, S.]] | + | [[Category: Muller-Loennies S]] |
| - | [[Category: Muniyappa, M.]] | + | [[Category: Muniyappa M]] |
| - | [[Category: Rudd, P M.]] | + | [[Category: Rudd PM]] |
| - | [[Category: Saldova, R.]] | + | [[Category: Saldova R]] |
| - | [[Category: Beta-sandwich]]
| + | |
| - | [[Category: Carbohydrate/sugar binding]]
| + | |
| - | [[Category: Immune system]]
| + | |
| Structural highlights
4m7j is a 2 chain structure with sequence from Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Method: | X-ray diffraction, Resolution 1.95Å |
| Ligands: | , , , , |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Publication Abstract from PubMed
The structure of the antigen-binding fragment of mAb S25-26 determined to 1.95 A resolution in complex with the Chlamydiaceae family-specific trisaccharide antigen Kdo(2-->8)-Kdo(2-->4)Kdo (Kdo=3-deoxy-alpha-D-manno-oct-2-ulopyranosonic acid) displays a germline-coded paratope that differs significantly from previously characterized Chlamydiaceae-specific mAbs, despite being raised against the identical immunogen. Unlike the terminal Kdo recognition pocket that promotes cross-reactivity in S25-2-type antibodies, S25-26 and the closely related S25-23 utilize a groove composed of germline residues to recognize the entire trisaccharide antigen and so confer strict specificity. Interest in S25-23 was sparked by its rare high muM affinity and strict specificity for the family-specific trisaccharide antigen; however, only the related antibody S25-26 proved amenable to crystallization. The structures of three unliganded forms of S25-26 have a labile complementary determining region H3 adjacent to significant glycosylation of the variable heavy chain on asparagine 85 in Framework Region 3. Analysis of the glycan reveals a heterogeneous mixture with a common root structure that contains an unusually high number of terminal alphaGal-Gal moieties. One of the few reported structures of glycosylated mAbs containing these epitopes is the therapeutic antibody Cetuximab; however, unlike Cetuximab, one of the unliganded structures in S25-26 shows significant order in the glycan with appropriate electron density for nine residues. The elucidation of the three dimensional structure of an alphaGal containing N-linked glycan on a mAb variable heavy chain has potential clinical interest, as they have been implicated in allergic response in patients receiving therapeutic antibodies.
Groove-type recognition of Chlamydiaceae-specific lipopolysaccharide antigen by a family of antibodies possessing an unusual variable heavy chain N-linked glycan.,Haji-Ghassemi O, Muller-Loennies S, Saldova R, Muniyappa M, Brade L, Rudd PM, Harvey DJ, Kosma P, Brade H, Evans SV J Biol Chem. 2014 Mar 28. PMID:24682362[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Haji-Ghassemi O, Muller-Loennies S, Saldova R, Muniyappa M, Brade L, Rudd PM, Harvey DJ, Kosma P, Brade H, Evans SV. Groove-type recognition of Chlamydiaceae-specific lipopolysaccharide antigen by a family of antibodies possessing an unusual variable heavy chain N-linked glycan. J Biol Chem. 2014 Mar 28. PMID:24682362 doi:http://dx.doi.org/10.1074/jbc.M113.528224
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