On molecular recognition of an uranyl chelate by monoclonal antibodies.
The energy landscape of the uranyl (UO2) chelate dissociated from a monoclonal antibody U08S was investigated using dynamic force spectroscopy (DFS). The uranyl ion (UO2(2+)) is chelated with the ligand dicarboxy-phenanthroline (DCP). The monoclonal antibody U08S was raised against UO2-DCP and does not cross-react with DCP alone. The results of plotting the most probable force against the logarithm of the loading rate show two distinguished values of slopes of multiple fitting lines, as observed in our previous study on that system with monoclonal antibody U04S (Odorico et al., 2007a. Biophys. J. 93: 645-654.). It indicates an unbinding process undergoing at least two activation states. We have generated the histogram of unbinding events with respect to the composite stiffness of the complex between the protein and the uranyl compound. Combining the model of Bell and Evans with that of Williams, we have estimated the number of parallel bonds involved in the unbinding process and determined the value of stiffness for individual bonds. We propose that the uranyl compound binds to the two antibodies U04S and U0c at structurally equivalent locations and forms the interaction with similar coordination modes. In addition, the unbinding process goes through two steps; the first weakens the bonding of the central metal with AspL50 of the antibody and the second breaks other non-bonded interactions of the compound with the antibody.
Teulon
Jean-Marie
JM
CEA VALRHO, DSV/iBEB/SBTN, BP 17171, 30207 Bagnols sur Cèze, France.
Odorico
Michael
M
Chen
Shu-wen W
SW
Parot
Pierre
P
Pellequer
Jean-Luc
JL
D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000378:metabolism*; D000915:Antibody Affinity; D000918:Antibody Specificity; D000937:Antigen-Antibody Reactions; D001666:Binding Sites, Antibody; D002614:Chelating Agents / Q000737:chemistry / Q000494:pharmacology; D006860:Hydrogen Bonding; D007700:Kinetics; D018625:Microscopy, Atomic Force; D008958:Models, Molecular; D010618:Phenanthrolines / Q000737:chemistry / Q000494:pharmacology*; D011485:Protein Binding; D017974:Uranium Compounds / Q000737:chemistry / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D002614:Chelating Agents; D010618:Phenanthrolines; D017974:Uranium Compounds