Braden B C, Poljak R J
Center for Advanced Research in Biotechnology, University of Maryland Biotechnology Institute, Rockville, Maryland 20850.
FASEB J. 1995 Jan;9(1):9-16. doi: 10.1096/fasebj.9.1.7821765.
Antibodies bind protein antigens over large sterically and electrostatically complementary surfaces. Van der Waals forces, hydrogen bonds, and occasionally ion pairs provide stability to antibody-antigen complexes. In addition, water molecules contribute hydrogen bonds linking antigen and antibody, and increase the complementarity of antigen-antibody interfaces. In qualification to a strict 'lock and key' mechanism, evidence of conformational changes between free and complexed antibodies indicate some accommodation to the antigen. Antibody-protein antigen reactions are enthalpically driven with varying degrees of entropic compensation, often dependent on the magnitude of the enthalpy of the reaction. In the case of two antibody-combining sites studied by X-ray diffraction, the relative arrangements of the variable domains of the light and heavy chains of the antibody change slightly from the free to the antigen-bound state. Furthermore, the contacting residues of both antibodies exhibit similar reduced mobilities when complexed to antigen, suggesting that differences in 'solvent entropy' rather than in conformational freedom may be the source of different entropic compensation factors. In concert, data from structural studies, reaction rates, calorimetric measurements, molecular dynamics simulations, and site-directed mutagenesis are beginning to detail the nature of antibody-protein antigen interactions.
抗体在空间和静电互补的大表面上结合蛋白质抗原。范德华力、氢键，偶尔还有离子对为抗体 - 抗原复合物提供稳定性。此外，水分子提供连接抗原和抗体的氢键，并增加抗原 - 抗体界面的互补性。与严格的“锁和钥匙”机制不同，游离抗体和结合抗原后的抗体之间构象变化的证据表明对抗原存在一定的适应性。抗体 - 蛋白质抗原反应由焓驱动，并伴有不同程度的熵补偿，这通常取决于反应焓的大小。在通过X射线衍射研究的两个抗体结合位点的情况下，抗体轻链和重链可变结构域的相对排列从游离状态到与抗原结合的状态略有变化。此外，两种抗体与抗原结合时，其接触残基均表现出类似的迁移率降低，这表明“溶剂熵”的差异而非构象自由度的差异可能是不同熵补偿因子的来源。同时，来自结构研究、反应速率、量热测量、分子动力学模拟和定点诱变的数据开始详细阐述抗体 - 蛋白质抗原相互作用的本质。
