Structure-function analysis and molecular modeling of DNase catalytic antibodies.

Immunology Letters
Haggag S ZeinKazutaka Miyatake

Abstract

There is great interest in the antibodies-to-DNA transformation, since this change is characteristic of autoimmune diseases and contributes to its pathology. After immunization and fusions, 14 hybridomas bearing DNA-hydrolysis activity against pUC19 plasmid DNA were obtained. Genes coding for V(H) and V(L) regions of the 14 monoclonal antibodies (mAbs) were cloned and sequenced. The sequences were compared with sequences of the Ig-Blast database to determine their germline and to identify potential mutations responsible for DNA binding and DNase activity. V genes of the H chains' genes expressed four genes of the V(H)1/J558 family, three of V(H)5/V(H)7183, and three of V(H)8/V(H)3609. The genetic repertoire of these mAbs was examined by determining the nucleotide sequences of their H chain V regions. This V(H) and V(L) domain was most similar to an anti-ssDNA (DNA-1) antibody as well as to catalytic autoimmune mAb (m3D8). Computer-generated models of the three-dimensional structures of V(H) and V(L) (VHL4) of the IgG4 combinations were used to define the positions occupied by the important sequence motifs at the binding sites. The modeling structure showed that VHL4 binds to oligo (dT3) primarily by sandwiching thymine bases be...Continue Reading

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Citations

Feb 14, 2012·Molecular Immunology·Damien Le MinouxSéverine Padiolleau-Lefèvre
Aug 4, 2011·Journal of Molecular Recognition : JMR·Haggag S ZeinKazutaka Miyatake

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Datasets Mentioned

BETA
EF672201

Methods Mentioned

BETA
PCR
X-ray

Software Mentioned

PyMol
IgBlast
Ig
WAM
AbM
BLAST
Pymol Molecular Graphics System
predict
ABI Prism Sequencing Analysis

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