Notch-Jagged complex structure implicates a catch bond in tuning ligand sensitivity
Vincent C. Luca(Howard Hughes Medical Institute), Byoung Choul Kim(Howard Hughes Medical Institute), Chenghao Ge(Georgia Institute of Technology), Shinako Kakuda(Stony Brook University), Di Wu(Howard Hughes Medical Institute), Mehdi Roein-Peikar(Howard Hughes Medical Institute), Robert S. Haltiwanger(Stony Brook University), Cheng Zhu(Georgia Institute of Technology), Taekjip Ha(Howard Hughes Medical Institute), K. Christopher García(Howard Hughes Medical Institute)
Cited by 300Open Access
Abstract
-Linked fucose modifications on Notch1 epidermal growth factor-like (EGF) domains 8 and 12 engage the EGF3 and C2 domains of Jag1, respectively, and different Notch1 domains are favored in binding to Jag1 than those that bind to the Delta-like 4 ligand. Jag1 undergoes conformational changes upon Notch binding, exhibiting catch bond behavior that prolongs interactions in the range of forces required for Notch activation. This mechanism enables cellular forces to regulate binding, discriminate among Notch ligands, and potentiate Notch signaling.
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