Taxonomic group: bacteria / Chlamydiae
(Phylum: Chlamydiae)
Associated disease: trachoma [ICD11:
1C23 
, ICD11:
XN4Q4 ];
infection due to Chlamydia trachomatis [ICD11:
XN4Q4 ];
infection due to Chlamydia [ICD11:
XN27H ]
NCBI PubMed ID: 24682362Publication DOI: 10.1074/jbc.M113.528224Journal NLM ID: 2985121RPublisher: Baltimore, MD: American Society for Biochemistry and Molecular Biology
Correspondence: sml
fz-borstel.de; svevans
uvic.ca
Institutions: From the Department of Biochemistry and Microbiology, University of Victoria, Victoria, British Columbia V8P 3P6, Canada, Research Center Borstel, Leibniz-Center for Medicine and Biosciences, Parkallee 22, Borstel D-23845, Germany
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-α-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 αGal-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 αGal 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.
antibodies, epitopes, MAb, Chlamydiaceae, N-linked glycan, lipopolysaccharide antigen
Structure type: oligomer
Location inside paper: abstract, p.16645
Trivial name: cross-reactive epitope
Compound class: core oligosaccharide, LPS
Contained glycoepitopes: IEDB_130650,IEDB_130657,IEDB_130658,IEDB_130659
Methods: X-ray, ELISA, ESI-MS, genetic methods, HPLC, crystallization, ITC
Comments, role: commerical synthetic trisaccharide. One of origins: Chlamydia sp. without species and strain assignment.
3D data: 3D data
Related record ID(s): 30243, 30244, 30245
NCBI Taxonomy refs (TaxIDs): 813,
810Reference(s) to other database(s): GlycomeDB:
5771
Show glycosyltransferases
There is only one chemically distinct structure:
Found 
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