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The inhibitory effect of an anti‐DPP IV monoclonal antibody 6A3 on the DPP IV/polymeric fibronectin adhesion is most likely due to a conformational change
Author(s) -
Cheng Hung-Chi,
Hung Ting-Ting,
Liu Ju-Fang,
Wu Jun-Yi
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.56.10
Subject(s) - fibronectin , epitope , dipeptidyl peptidase , chemistry , monoclonal antibody , microbiology and biotechnology , amino acid , binding site , biochemistry , conformational change , enzyme , stereochemistry , antibody , cell , biology , immunology
The epitope of an anti‐rat endothelial Dipeptidyl peptidase IV (DPP IV) monoclonal antibody (mAb) 6A3, capable of inhibiting polymeric fibronectin (polyFN)‐mediated lung‐metastatic cancer cell adhesion to DPP IV, has been mapped to D 329 KTTLVWN of rDPP IV in close proximity to L 311 QWLRRI, the putative FN‐binding motif. There has, however, never been direct evidence in confirming this putative motif. For that purpose, the pulldown assay for various DPP IV fragments with polyFN‐conjugated gelatin beads was performed. Surprisingly, fragments harboring L 311 QWLRRI did not show any significant binding activity, whereas N‐terminal fragments excluding L 311 QWLRRI strongly bound to polyFN. Since the 6A3 epitope‐equivalent domain is structurally located within the adenosine deaminase (ADA)‐binding region of hDPP IV, binding of 6A3 may mimic that of ADA. Upon superimposition of the rDPP IV structure with that of either hDPP IV or ADA‐bound hDPP IV, the overall structural similarities were extremely high, except one apparent difference within an approximately 10 amino acid‐region between naked DPP IVs and ADA‐bound hDPP IV near their N‐terminals. We therefore re‐hypothesize that 6A3 causes a conformational change of this newly proposed 10 amino acid FN‐binding motif of DPP IV in inhibiting DPP IV/polyFN binding. This study was supported by NSC 99‐2320‐B‐006 ‐028 ‐MY3 and NSC 99‐2627‐B‐006‐023.