Fig. 7
From: Domain-interface dynamics of CFTR revealed by stabilizing nanobodies
NBD1 must undock from the TMDs to allow binding of nanobodies T4 or T8. Current models indicate that CFTR alternates between a state where the two NBDs are in close contact (state a), leading to channel opening, and a state where the NBDs separate leading to channel closing (state b). State a would typically be induced by PKA phosphorylation. States a and b have been observed by cryo-EM and both bury F508 in the NBD1-TMD interface. Nanobodies T4 and T8 bind an epitope containing F508 (illustrated in red), thus requiring a transient undocking of NBD1 from the TMDs (state c). This transient state can be stabilized upon binding of these nanobodies (state d)
