Figure 1

Tetraspanin topology and open-/closed-conformation. Tetraspanin embedded into a membrane bilayer; top and bottom correspond to the extracellular and intracellular side, respectively. (A) Schematic depiction of the tetraspanin’s topology including four transmembrane segments (TMS1–4), a small extracellular loop (SEL) and a large extracellular loop (LEL, shown with the conserved helical domains A,B,E), a small intracellular loop (SIL) and a N and C terminus. This illustration was modified from Hochheimer et al.¹¹. (B) Different conformations proposed for CD81 referred to as helix bundle/’open’ (left, based on PDB: 7JIC) and funnel shape/’closed’ (right, basd on PDB: 5TCX) that differ in the arrangement of the TMSs and the orientation of the LEL; the right structure represents the closed conformation as defined by Zimmerman et al.¹². The scheme was created using CorelDRAW 2019 (www.corel.com) and the cryo-EM and crystal structure images were created using PyMOL 2.5 (https://pymol.org/2/).