Fig. 8: Proposed gating mechanism of TrkHA.

Upper: Cartoon illustration of TrkHA in the closed (left) and open (right) states viewed within the plane of the membrane (gray). Teal and cyan: TrkH; blue: N2 domain; purple: N1 domain; light blue: C2 domain; and light purple: C1. The green outlines mark one TrkH and one TrkA protomer. Lower: the tetrameric TrkA ring in the presence of ATP (left) and the two TrkA dimers in the presence of ATP (right). In the presence of ADP, TrkA forms a tetramer and closes TrkH through interactions at both the HN1 and HN2 interfaces. In the presence of ATP, the tetrameric TrkA gating ring is split into two dimers. Opening of a TrkH channel is achieved by the downward movement of the N2 domains away from the membrane that in turn moves the intramembrane loop from blocking the selectivity filter, and by distruption of the HN1 interfaces that allows dilation of the pore-lining helices. The two TrkH protomers also rotate relative to each other during the gating process.