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Participated in manuscript preparation; H.Z., L.-N.C., J.Q., D.-D.S., and C.M. Performed specimen screening, cryo-EM grid preparation, data collection; H.Z. Processed the cryo-EM data, modeled, and refined the structures from cryo-EM density maps; H.Z. Performed structural analysis and figure preparation; https://cck444.com/ H.Z., Y.D., Y.-Y.L., L.-N.C., and S.-Y.J.

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  • Fetal mice express high levels of CCK mRNA in cardiac myocytes (112).
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  • The outward movement of TM6 is a hallmark of receptor activation and the various extent of the TM6 openness relative to other TMs was proposed to be the determinants of G protein subtype specificity47,48.
  • Performed structural analysis and figure preparation; H.Z., Y.D., Y.-Y.L., L.-N.C., and S.-Y.J.

Remarkably, the expression in diabetic mice and rat kidneys is grossly increased. This increase has been suggested to protect the diabetic kidneys somewhat against inflammatory actions of macrophages (103). Pituitary corticotrophs and melanotrophs express significant amounts of proCCK fragments, but the posttranslational processing results in only trace amounts of conventional α-amidated CCK peptides (43, 96). Also, thyroid C-cells produce CCK, but mainly as non-sulfated but amidated CCK-8 (17). Since C-cells are well equipped with CCK2 receptors (97), thyroid CCK-8 is probably an autocrine stimulator of growth of normal and not least malignant C-cells.

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