Journal
JOURNAL OF BIOLOGICAL CHEMISTRY
Volume 289, Issue 24, Pages 16644-16661Publisher
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.M113.528224
Keywords
-
Categories
Funding
- Natural Sciences and Engineering Research Council of Canada
- European Union [260600]
- Fonds zur Forderung der wissenschaftlichen Forschung [P22909]
- Michael Smith Foundation for Health Research Senior Scholarship
- Austrian Science Fund (FWF) [P22909] Funding Source: Austrian Science Fund (FWF)
Ask authors/readers for more resources
The structure of the antigen binding fragment ofmAb S25-26, determined to 1.95 angstrom 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 germ-line-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 germ-line residues to recognize the entire trisaccharide antigen and so confer strict specificity. Interest in S25-23 was sparked by its rare high mu M 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 alpha Gal-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 alpha Gal-containing N-linked glycan on a mAb variable heavy chain has potential clinical interest, as it has been implicated in allergic response in patients receiving therapeutic antibodies.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available