A functional-phylogenetic classification system for transmembrane solute transporters

Abstract

A comprehensive classification system for transmembrane molecular transporters has been developed and recently approved by the transport panel of the nomenclature committee of the International Union of Biochemistry and Molecular Biology. This system is based on (i) transporter class and subclass (mode of transport and energy coupling mechanism), (ii) protein phylogenetic family and subfamily, and (iii) substrate specificity. Almost all of the more than 250 identified families of transporters include members that function exclusively in transport. Channels (115 families), secondary active transporters (uniporters, symporters, and antiporters) (78 families), primary active transporters (23 families), group translocators (6 families), and transport proteins of ill-defined function or of unknown mechanism (51 families) constitute distinct categories. Transport mode and energy coupling prove to be relatively immutable characteristics and therefore provide primary bases for classification. Phylogenetic grouping reflects structure, function, mechanism, and often substrate specificity and therefore provides a reliable secondary basis for classification. Substrate specificity and polarity of transport prove to be more readily altered during evolutionary history and therefore provide a tertiary basis for classification. With very few exceptions, a phylogenetic family of transporters includes members that function by a single transport mode and energy coupling mechanism, although a variety of substrates may be transported, sometimes with either inwardly or outwardly directed polarity. In this review, I provide cross-referencing of well-characterized constituent transporters according to (i) transport mode, (ii) energy coupling mechanism, (iii) phylogenetic grouping, and (iv) substrates transported. The structural features and distribution of recognized family members throughout the living world are also evaluated. The tabulations should facilitate familial and functional assignments of newly sequenced transport proteins that will result from future genome sequencing projects.

FIG. 1

Scheme illustrating the currently recognized primary types of transporters found in nature. These proteins are initially divided into channels and carriers. Channels are subdivided into α-helical protein channels, β-barrel protein porins (mostly in the outer membranes of gram-negative bacteria and eukaryotic organelles), toxin channels, and peptide channels. Carriers are subdivided into primary active carriers, secondary active carriers (including uniporters), and group translocators that modify their substrates during transport. Primary sources of chemical energy that can be coupled to transport include pyrophosphate bond (i.e., ATP) hydrolysis, decarboxylation, and methyl transfer. Oxidation-reduction reactions, light absorption, and mechanical devices can also be coupled to transport (see text). Secondary active transport is driven by ion and other solute (electro)chemical gradients created by primary active transport systems. The only well-established group-translocating system found in nature is the bacterial phosphoenolpyruvate:sugar PTS, which phosphorylates its sugar substrates during transport.

FIG. 2

Established or predicted topologies for channel proteins (A), carrier proteins (B), and proteins of unknown transport mode (C). The proteins included in A are the channel proteins of TC category 1.A, while the carriers represented in B are the families of TC category 2.1A. Because most primary carriers of categories 3 consist of heterooligomers, many of very complex structure, these were not included in the analyses depicted.