Braden B C, Goldman E R, Mariuzza R A, Poljak R J
Center for Advanced Research in Biotechnology, University of Maryland Biotechnology Institute, Rockville, USA.
Immunol Rev. 1998 Jun;163:45-57. doi: 10.1111/j.1600-065x.1998.tb01187.x.
Using site-directed mutagenesis, x-ray crystallography, microcalorimetric, equilibrium sedimentation and surface plasmon resonance detection techniques, we have examined the structure of an antibody-antigen complex and the structural and thermodynamic consequences of removing specific hydrogen bonds and van der Waals interactions in the antibody-antigen interface. These observations show that the complex is considerably tolerant, both structurally and thermodynamically, to the truncation of antibody and antigen side chains that form contacts. Alterations in interface solvent structure for two of the mutant complexes appear to compensate for the unfavorable enthalpy changes when antibody-antigen interactions are removed. These changes in solvent structure, along with the increased mobility of side chains near the mutation site, probably contribute to the observed entropy compensation. In concert, data from structural studies, reaction rates, calorimetric measurements and site directed mutations are beginning to detail the nature of antibody-protein antigen interactions.
利用定点诱变、X射线晶体学、微量量热法、平衡沉降和表面等离子体共振检测技术，我们研究了抗体-抗原复合物的结构，以及去除抗体-抗原界面中特定氢键和范德华相互作用的结构和热力学后果。这些观察结果表明，该复合物在结构和热力学上对形成接触的抗体和抗原侧链的截断具有相当的耐受性。当去除抗体-抗原相互作用时，两种突变复合物的界面溶剂结构变化似乎补偿了不利的焓变。溶剂结构的这些变化，以及突变位点附近侧链流动性的增加，可能导致了观察到的熵补偿。综合来看，来自结构研究、反应速率、量热测量和定点突变的数据开始详细阐述抗体-蛋白质抗原相互作用的本质。
