Reference : The indirect generation of long-distance structural changes in antibodies upon their ...
Scientific journals : Article
Life sciences : Biochemistry, biophysics & molecular biology
The indirect generation of long-distance structural changes in antibodies upon their binding to antigen
Piekarska, Barbara [> >]
Drozd, Anna [> >]
Konieczny, Leszek [> >]
Krol, Marcin [> >]
Jurkowski, Wiktor [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > >]
Roterman, Irena [> >]
Spolnik, Pawel [> >]
Stopa, Barbara [> >]
Rybarska, Janina [> >]
Chemical Biology and Drug Design
Blackwell Publishing
Yes (verified by ORBilu)
[en] An allosteric mechanism for the generation of long-distance structural alterations in Fab fragments of antibodies in immune complexes has been postulated and tested in theoretical and experimental analysis. The flexing and/or torsion-derived forces exerted on the elbow region in Fab arms of bivalent antibodies upon binding to antigen were assumed to drive the disruption of hydrogen bonds which stabilize N- and C-terminal chain fragments in V-domains. This allows an extra movement in the elbow followed by a relaxation in the Fab arm and may generate long-distance effects if, in particular, the structural changes are generated asymmetrically involving one chain of the Fab arm only. This mechanism was studied by simulation of molecular dynamics. The local instability in the area involving the site of packing of the N-terminal chain fragment allows penetration and binding of the supramolecular dye Congo red that hence becomes an indicator of the initiated relaxation process and is also the prospective ligand in studies of designing drugs. The susceptibility to dye binding was observed in complexation of bivalent antibodies only, supplying the evidence that constraints associating the interaction with randomly distributed antigenic determinants drive the local structural changes in the V-domain followed by long-distance effects.

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