Fig. 5: EMC binding reorients transmembrane domains.

a Analysis of the TMD tilt towards membrane normal throughout molecular dynamics simulations (5 replicas for simulations in complex with EMC, and 1 replica for the free transmembrane domain simulations, 100 ns simulation time per replica with tilt data collected every 200 ps) of selected ConMem variants in isolation (gray) and bound to the EMC1 chaperone site (red). Simulated TMDs with a high experimental EMC binding affinity (right) are tilted to higher angles in isolation, which is significantly reduced upon EMC binding. In contrast, the tilt angle of weak binders is not strongly affected by EMC binding (left). b Tilt angle analysis as in a, for TMD3 of SLC4A2, which was identified in Fig. 3c as a strong endogenous EMC binding transmembrane sequence. Please note that the topology of this protein is not well defined, and we show the one consistent with Uniprot annotation here, yet we cannot exclude a different orientation of the TMDs, which would affect our findings.