Extended Data Fig. 8: Changes of inter-subunit contacts at the MHR domains between closed and open states.

Two neighboring hTRPM4 subunits are shown in cartoon representation with the inter-subunit contact regions colored red. In the closed state (top), the MHR domains make two loose inter-subunit contacts: one contact, proximal to the membrane, is between the loop connecting helices 3 & 4 of MHR4 and the loop connecting helices 4 & 5 in the neighboring MHR4; the other contact, distal to the membrane, is between loops in MHR1 (β3-4 loop and post-β7 loop) and loops in MHR3 from the neighboring subunit (loops between helices 4 & 5 and between helices 6 & 7). In the open state (bottom), the upward swing of the MHR domains renders a new membrane-proximal contact between the turn of helices 3 & 4 from MHR4 and helix 7 of the neighboring MRH4 and a more extensive membrane-distal contact between the MHR1 and MHR2 domains (N-terminus of MHR1 helix 2, N-terminus of MHR2 helix 3 and C-terminus of MHR2 helix4) and the MHR3 domain from the neighboring subunit (C-terminus of helix 6 and the loop between helices 4 and 5).