STRUCTURAL EVIDENCE FOR INDUCED FIT AS A MECHANISM FOR ANTIBODY-ANTIGEN RECOGNITION

被引:512
作者
RINI, JM [1 ]
SCHULZEGAHMEN, U [1 ]
WILSON, IA [1 ]
机构
[1] Scripps Res Inst, RES INST, DEPT MOLEC BIOL, 10666 N TORREY PINES RD, LA JOLLA, CA 92037 USA
关键词
D O I
10.1126/science.1546293
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
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页码:959 / 965
页数:7
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