Six-transmembrane helical domain (TmrB) of the heterodimeric Thermus thermophilus multidrug resistance proteins TmrAB, and similar proteins
This group represents the six-transmembrane helical domain (6-TMD) of the heterodimeric Thermus thermophilus multidrug resistance proteins A and B (TmrAB), a homolog of the Antigen Translocation Complex Tap, and similar proteins. TmrAB has been shown to able to restore antigen processing in human TAP-deficient cells. The 6-transmembrane (TM) helices typically found in the ATP-binding cassette (ABC) transporters that function as exporters, which contain 6 TM helices per subunit (domain), or a total of 12 TM helices for the complete transporter. The ABC exporters are found in both prokaryotes and eukaryotes, where they mediate the cellular secretion of toxic compounds and a various type of lipids. ABC transporters typically consist of two transmembrane domains (TMDs) and two nucleotide-binding domains (NBDs). The sequences and structures of the TMDs are quite varied between the different type of transporters, suggesting significant structural diversity of the translocated substrates, while NBDs are conserved among all ABC transporters. The two NBDs together bind and hydrolyze ATP, thereby providing the driving force for transport, while the TMDs participate in substrate recognition and translocation across the lipid membrane. However, some ABC genes are organized as half-transporters, which must form either homodimers or heterodimers to form a functional transporter. The ABC exporters play a role in multidrug resistance to antibiotics and anticancer agents, and mutations in these proteins have been shown to cause severe human diseases such as cystic fibrosis.
Structure:5MKK; TmrB of the Thermus thermophilus heterodimeric multidrug ABC transport complex TmrAB shows an inward-facing open conformation, contacts at 4A.
Comment:TmrAB consists of two nucleotide-binding domains (NBDs), which bind and hydrolyze ATP, and two transmembrane domains (TMDs) that facilitate substrate translocation.
Jiyao W et al.(2023). "The conserved domain database in 2023.",