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| | <StructureSection load='4m93' size='340' side='right'caption='[[4m93]], [[Resolution|resolution]] 2.09Å' scene=''> | | <StructureSection load='4m93' size='340' side='right'caption='[[4m93]], [[Resolution|resolution]] 2.09Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4m93]] is a 4 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=4M93 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4M93 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4m93]] is a 4 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=4M93 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4M93 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=PCA:PYROGLUTAMIC+ACID'>PCA</scene></td></tr> |
| - | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=PCA:PYROGLUTAMIC+ACID'>PCA</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=4m93 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4m93 OCA], [https://pdbe.org/4m93 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4m93 RCSB], [https://www.ebi.ac.uk/pdbsum/4m93 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4m93 ProSAT]</span></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4m7j|4m7j]], [[4ma1|4ma1]], [[4m7z|4m7z]]</td></tr>
| + | |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4m93 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4m93 OCA], [http://pdbe.org/4m93 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4m93 RCSB], [http://www.ebi.ac.uk/pdbsum/4m93 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4m93 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
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| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| | [[Category: Mus musculus]] | | [[Category: Mus musculus]] |
| - | [[Category: Evans, S V]] | + | [[Category: Evans SV]] |
| - | [[Category: Haji-Ghassemi, O]] | + | [[Category: Haji-Ghassemi O]] |
| - | [[Category: Carbohydrate/sugar binding]]
| + | |
| - | [[Category: Immune system]]
| + | |
| Structural highlights
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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