Lipid transporters play an important role in most if not all organisms,
ranging from bacteria to humans. For example, in Mycobacterium
tuberculosis, the trehalose monomycolate transporter MmpL3 is involved
in cell wall biosynthesis, while in humans, cholesterol transporters are
involved in normal cell function as well as in disease. Here, using
structural and bioinformatics information, we propose that there are
proteins that also contain “MmpL3-like” (MMPL) transmembrane (TM)
domains in many protozoa, including Trypanosoma cruzi, as well as
in the bacterium Staphylococcus aureus, where the fatty acid
transporter FarE has the same set of “active-site” residues as those
found in the mycobacterial MmpL3s, and in T. cruzi. We also show
that there are strong sequence and predicted structural similarities
between the TM proton-translocation domain seen in the X-ray structures
of mycobacterial MmpL3s and several human as well as fungal lipid
transporters, leading to the proposal that there are similar proteins in
apicomplexan parasites, and in plants. The animal, fungal, apicomplexan
and plant proteins have larger extra-membrane domains than are found in
the bacterial MmpL3, but they have a similar TM domain architecture,
with the introduction of a (catalytically essential)
Phe>His residue change, and a Ser/Thr H-bond network,
involved in H -transport. Overall, the results are of
interest since they show that MMPL-family proteins are present in
essentially all life-forms: archaea, bacteria, protozoa, fungi, plants
and animals and, where known, they are involved in “lipid”
(glycolipid, phospholipid, sphingolipid, fatty acid, cholesterol,
ergosterol) transport, powered by transmembrane molecular pumps having
similar structures.