The major facilitator superfamily (MFS) represents the largest collection o
f evolutionarily related members within the class of membrane 'carrier' pro
teins. OAT, a representative example of the MFS, is an oxalate-transporting
membrane protein in Oxalobacter formigenes. From an electron crystallograp
hic analysis of two-dimensional crystals of OAT, we have determined the pro
jection structure of this membrane transporter. The projection map at 6 Ang
strom resolution indicates the presence of 12 transmembrane helices in each
monomer of OxlT, with one set of six helices related to the other set by a
n approximate internal two-fold axis. The projection map reveals the existe
nce of a central cavity, which we propose to be part of the pathway of oxal
ate transport. By combining information from the projection map with relate
d biochemical data, we present probable models for the architectural arrang
ement of transmembrane helices in this protein superfamily.