1VFA

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

1VFA の概要

• エントリーDOI: 10.2210/pdb1vfa/pdb
• 分子名称: IGG1-KAPPA D1.3 FV (LIGHT CHAIN), IGG1-KAPPA D1.3 FV (HEAVY CHAIN) (3 entities in total)
• 機能のキーワード: immunoglobulin
• 由来する生物種: Mus musculus (house mouse); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 24715.45

構造登録者

Bhat, T.N.,Poljak, R.J. (登録日: 1993-12-03, 公開日: 1994-05-31, 最終更新日: 2024-10-30)

主引用文献

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

実験手法

X-RAY DIFFRACTION (1.8 Å)