STRUCTURAL EVIDENCE FOR INDUCED FIT AS A MECHANISM FOR ANTIBODY-ANTIGEN RECOGNITION
STRUCTURAL EVIDENCE FOR INDUCED FIT AS A MECHANISM FOR ANTIBODY-ANTIGEN RECOGNITION
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DOI：
10.1126/science.1546293
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发表时间：
1992-02-21
期刊：
影响因子：
56.9
通讯作者：
WILSON, IA
中科院分区：
文献类型：
--
作者：
RINI, JM;SCHULZEGAHMEN, U;WILSON, IA
流感病毒血凝素 [HA1(75-110)] 肽免疫原的特异性抗体 (Fab 17/9) 的三维结构以及该抗体与结合肽 (Tyr(P100)-Leu(P108) 的两个独立晶体复合物已通过 X 射线晶体学技术分别在 2.0 埃、2.9 埃和 3.1 埃分辨率下测定。九肽抗原在抗体结合位点呈现 I 型 β 转角，并主要与 Fab 高变环 L3、H2 和 H3 相互作用。比较结合和未结合的 Fab 结构表明，H3 环中的主要重排伴随着抗原结合，导致肽的 β 转角形成结合袋，从而适应与抗体结合的肽的构象。游离抗体和抗原结合抗体的结构证明了抗体结合位点的灵活性，并提供了诱导契合作为抗体-抗原识别机制的例子。
The three-dimensional structure of a specific antibody (Fab 17/9) to a peptide immunogen from influenza virus hemagglutinin [HA1(75-110)] and two independent crystal complexes of this antibody with bound peptide (Tyr(P100)-Leu(P108) have been determined by x-ray crystallographic techniques at 2.0 angstrom, 2.9 angstrom, and 3.1 angstrom resolution, respectively. The nonapeptide antigen assumes a type I beta-turn in the antibody combining site and interacts primarily with the Fab hypervariable loops L3, H2, and H3. Comparison of the bound and unbound Fab structures shows that a major rearrangement in the H3 loop accompanies antigen binding. This conformational change results in the creation of a binding pocket for the beta-turn of the peptide, allowing Tyr(P105) to be accommodated. The conformation of the peptide bound to the antibody shows similarity to its cognate sequence in the HA1, suggesting a possible mechanism for the cross-reactivity of this Fab with monomeric hemagglutinin. The structures of the free and antigen bound antibodies demonstrate the flexibility of the antibody combining site and provide an example of induced fit as a mechanism for antibody-antigen recognition.