X-ray snapshots of the maturation of an antibody response to a protein antigen
X-ray snapshots of the maturation of an antibody response to a protein antigen
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DOI：
10.1038/nsb930
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发表时间：
2003-06-01
期刊：
影响因子：
--
通讯作者：
Mariuzza, RA
中科院分区：
文献类型：
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作者：
Li, YL;Li, HM;Mariuzza, RA
免疫系统在对抗原的应答过程中产生更高亲和力的抗体（亲和力成熟）的过程是分子进化的典型例子。早期的研究仅限于对小分子（半抗原）而不是蛋白质具有特异性的抗体。我们比较了四种抗体在亲和力成熟的不同阶段与鸡蛋白色溶菌酶（HEL）上相同位点结合的结构。这些X-射线快照显示，结合增强，而不是通过形成额外的氢键或货车德瓦尔斯接触或增加总掩埋表面，但通过掩埋的非极性表面的增加量的极性表面的牺牲，伴随着改进的形状互补性。疏水相互作用的增加是由于界面外围抗体残基的高度相关重排，与中心能量热点相邻。这第一次可视化的成熟抗体蛋白质提供了深入了解其他蛋白质蛋白质界面的高亲和力的演变。
The process whereby the immune system generates antibodies of higher affinities during a response to antigen ( affinity maturation) is a prototypical example of molecular evolution. Earlier studies have been confined to antibodies specific for small molecules (haptens) rather than for proteins. We compare the structures of four antibodies bound to the same site on hen egg white lysozyme (HEL) at different stages of affinity maturation. These X-ray snapshots reveal that binding is enhanced, not through the formation of additional hydrogen bonds or van der Waals contacts or by an increase in total buried surface, but by burial of increasing amounts of apolar surface at the expense of polar surface, accompanied by improved shape complementarity. The increase in hydrophobic interactions results from highly correlated rearrangements in antibody residues at the interface periphery, adjacent to the central energetic hot spot. This first visualization of the maturation of antibodies to protein provides insights into the evolution of high affinity in other protein protein interfaces.