Transmembrane domain 1 (TMD1)

Transmembrane domain 1 (TMD1) is a structural alpha-helical segment found at the N-terminus of many integral membrane proteins, including G protein-coupled receptors (GPCRs), ion channels, and transporters. While not a standalone protein, TMD1 is a critical site for pharmacological intervention in several major diseases. In cystic fibrosis, TMD1 of the CFTR protein is the primary binding site for corrector drugs like Lumacaftor, which facilitate the proper folding and trafficking of the mutant protein to the cell surface. In Alzheimer's disease research, TMD1 of Presenilin 1 is recognized as a vital component of the gamma-secretase catalytic pore and a target for inhibitors designed to reduce amyloid-beta production. Additionally, structural studies of viral proteins like LMP1 and host proteins like IFITM1 highlight TMD1 as a mediator of signaling and viral entry, making it a focal point for developing novel anti-infective and anti-cancer agents.

Other names

TM1First transmembrane helixTransmembrane segment 1