Cryo-EM structure of human TMEM45B with a bound GM3 (18:1;O2/24:1).

The orphan transmembrane protein 45B (TMEM45B) has been reported to be involved in mechanical pain hypersensitivity, antiviral processes, and cancer. The structure of human TMEM45B with bound monosialodihexosylganglioside (GM3, 18:1;O2/24:1), presented here, determined by single-particle cryo-electron microscopy (cryo-EM) to 2.8 Å, reveals a homotetrameric assembly of seven-transmembrane-helix protomers. The first six transmembrane helices from each protomer create a central hydrophobic tunnel that accommodates metal ions and the C24:1 fatty acid component of the ganglioside GM3.