1VFB

BOUND WATER MOLECULES AND CONFORMATIONAL STABILIZATION HELP MEDIATE AN ANTIGEN-ANTIBODY ASSOCIATION

Summary for 1VFB

• Entry DOI: 10.2210/pdb1vfb/pdb
• Descriptor: IGG1-KAPPA D1.3 FV (LIGHT CHAIN), IGG1-KAPPA D1.3 FV (HEAVY CHAIN), HEN EGG WHITE LYSOZYME, ... (4 entities in total)
• Functional Keywords: immunoglobulin/hydrolase(o-glycosyl), immunoglobulin-hydrolase(o-glycosyl) complex
• Biological source: Mus musculus (house mouse); More
• Cellular location: Secreted: P00698
• Total number of polymer chains: 3
• Total formula weight: 38889.41

Authors

Bhat, T.N.,Poljak, R.J. (deposition date: 1993-12-03, release date: 1994-05-31, Last modification date: 2024-11-20)

Primary citation

Bhat, T.N.,Bentley, G.A.,Boulot, G.,Greene, M.I.,Tello, D.,Dall'Acqua, W.,Souchon, H.,Schwarz, F.P.,Mariuzza, R.A.,Poljak, R.J.
Bound water molecules and conformational stabilization help mediate an antigen-antibody association.
Proc.Natl.Acad.Sci.USA, 91:1089-1093, 1994

PubMed Abstract: We report the three-dimensional structures, at 1.8-A resolution, of the Fv fragment of the anti-hen egg white lysozyme antibody D1.3 in its free and antigen-bound forms. These structures reveal a role for solvent molecules in stabilizing the complex and provide a molecular basis for understanding the thermodynamic forces which drive the association reaction. Four water molecules are buried and others form a hydrogen-bonded network around the interface, bridging antigen and antibody. Comparison of the structures of free and bound Fv fragment of D1.3 reveals that several of the ordered water molecules in the free antibody combining site are retained and that additional water molecules link antigen and antibody upon complex formation. This solvation of the complex should weaken the hydrophobic effect, and the resulting large number of solvent-mediated hydrogen bonds, in conjunction with direct protein-protein interactions, should generate a significant enthalpic component. Furthermore, a stabilization of the relative mobilities of the antibody heavy- and light-chain variable domains and of that of the third complementarity-determining loop of the heavy chain seen in the complex should generate a negative entropic contribution opposing the enthalpic and the hydrophobic (solvent entropy) effects. This structural analysis is consistent with measurements of enthalpy and entropy changes by titration calorimetry, which show that enthalpy drives the antigen-antibody reaction. Thus, the main forces stabilizing the complex arise from antigen-antibody hydrogen bonding, van der Waals interactions, enthalpy of hydration, and conformational stabilization rather than solvent entropy (hydrophobic) effects.

PubMed: 8302837
DOI: 10.1073/pnas.91.3.1089

Experimental method

X-RAY DIFFRACTION (1.8 Å)