International
Tables for
Crystallography
Volume F
Crystallography of biological macromolecules
Edited by M. G. Rossmann and E. Arnold

International Tables for Crystallography (2006). Vol. F. ch. 23.4, p. 638   | 1 | 2 |

Section 23.4.6.1. Antigen–antibody association

C. Mattosa* and D. Ringeb

aDepartment of Molecular and Structural Biochemistry, North Carolina State University, 128 Polk Hall, Raleigh, NC 02795, USA, and  bRosenstiel Basic Medical Sciences Research Center, Brandeis University, 415 South St, Waltham, MA 02254, USA
Correspondence e-mail:  mattos@bchserver.bch.ncsu.edu

23.4.6.1. Antigen–antibody association

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The X-ray crystal structures of the Fv fragment of the monoclonal antibody D1.3 and the structure of its complex with hen egg-white lysozyme were both solved to 1.8 Å resolution (Bhat et al., 1994[link]). This study revealed a significant number of water molecules contributing to the chemical complementarity at the antigen–antibody interface. There are 23 water molecules at the antigen-binding site of the free antibody fragment, while 48 are present mediating complex formation. Seven water molecules are in equivalent positions in the free and complexed antibody (within 1.5 Å). There is no net loss of water molecules at the combining site. In fact, the total number of water molecules at the antigen–antibody interface is not less, but more, than the sum of those in the free antibody combining site and in the antigenic determinant. Furthermore, there is a general decrease in B factors of the binding-site residues upon complex formation, implying a decrease in entropy (Bhat et al., 1994[link]). The structural results indicate that water molecules at the antigen–antibody interface play a variety of important roles. Some form an integral part of the active site, fine-tuning the shape and charge complementarity of the interaction. Others are found to be displaced during complex formation, and still others are unique to the complex, bridging between the two molecules in a variety of locations throughout the complex interface.

The structural analysis correlated well with results of calorimetric experiments that showed that complex formation is enthalpically driven, with an unfavourable entropic contribution (Bhat et al., 1994[link]). The authors suggest that water molecules play a central role in mediating complex formation and claim that the hydrophobic effect is not important in this case. This is an argument that goes contrary to the idea that affinity is contributed by hydrophobic interactions within a relatively small portion of the interface between the interacting molecules, with hydrogen-bonding and charge–charge interactions contributing primarily to specificity (Hendsch & Tidor, 1994[link]; Clackson & Wells, 1995[link]; Hendsch et al., 1996[link]).

References

First citation Bhat, T. N., Bentley, G. A., Boulot, G., Greene, M. I., Tello, D., Dall'Acqua, W., Souchon, H., Schwarz, F. P., Maiuzza, R. A. & Poljak, R. J. (1994). Bound water molecules and conformational stabilization help mediate an antigen–antibody association. Proc. Natl Acad. Sci. USA, 91, 1089–1093.Google Scholar
First citation Clackson, T. & Wells, J. T. (1995). A hot spot of binding energy in a hormone–receptor interface. Science, 267, 383–386.Google Scholar
First citation Hendsch, Z. S., Jonsson, T., Sauer, R. T. & Tidor, B. (1996). Protein stabilization by removal of unsatisfied polar groups: computational approaches and experimental tests. Biochemistry, 35, 7621–7625.Google Scholar
First citation Hendsch, Z. S. & Tidor, B. (1994). Do salt bridges stabilize proteins? A continuum electrostatic analysis. Protein Sci. 3, 211–226.Google Scholar








































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