Article
Mechanical force regulates ligand binding and function of PD-1.
Nature communications - 27 Sept 2024
Li Kaitao, Cardenas-Lizana Paul, Lyu Jintian, Kellner Anna V, Li Menglan, Cong Peiwen, Watson Valencia E, Yuan Zhou, Ahn Eunseon, Doudy Larissa, Li Zhenhai, Salaita Khalid, Ahmed Rafi, Zhu Cheng
Abstract excerpt
Despite the success of PD-1 blockade in cancer therapy, how PD-1 initiates signaling remains unclear. Soluble PD-L1 is found in patient sera and can bind PD-1 but fails to suppress T cell function. Here, we show that PD-1 function is reduced when mechanical support on ligand is removed. Mechanistically, cells exert forces to PD-1 and prolong bond lifetime at forces <7 pN (catch bond) while accelerate dissociation...
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