Recent experiments in bacterial systems have established an extended d
atabase of sequences broadly relevant to all membrane transporters, al
lowing serious study of evolutionary relationships. The database will
be especially useful in integrating conclusions derived from work with
proteins in the major facilitator superfamily, because this kinship i
ncludes both eukaryotic and prokaryotic model systems. Even among carr
iers not linked by evolution, clear hints of functional homology have
been noted. Advances are also evident in the structural analysis of me
mbrane carriers. Site-directed mutagenesis in a bacterial antiporter h
as shown how the translocation pathway might be identified; this shoul
d complement recent progress in preparing two-dimensional crystals of
the eukaryotic anion-exchange protein, band 3. Together, these studies
could soon verify or reject the idea that the transport pathway lies
at the interface between the amino-terminal and carboxy-terminal helic
al bundles found in the hydrophobic core of most carrier proteins. If
verified, the argument might allow construction of informed three-dime
nsional models in the absence of crystallographic evidence.