The Amino Acid-Polyamine-Organocation Superfamily

Abstract

The amino acid-polyamine-organocation (APC) superfamily has been shown to include five recognized families, four of which are specific for amino acids and their derivatives. Recent high-resolution X-ray crystallographic data have shown that four additional transporter families (BCCT, TC No. 2.A.15; SSS, 2.A.21; NSS, 2.A.22; and NCS1, 2.A.39), transporting a wide range of solutes, exhibit sufficiently similar folds to suggest a common evolutionary origin. We have used established statistical methods, based on sequence similarity, to show that these families are, in fact, members of the APC superfamily. We also identify two additional families (NCS2, 2.A.40; SulP, 2.A.53) as being members of this superfamily. Repeat sequences, each having five transmembrane α-helical segments and arising via ancient intragenic duplications, are demonstrated for all of these families, further strengthening the conclusion of homology. The APC superfamily appears to be the second largest superfamily of secondary carriers, the largest being the major facilitator superfamily (MFS). Although the topology of the members of the APC superfamily differs from that of the MFS, both families appear to have arisen from a common ancestral 2 TMS hairpin structure that underwent intragenic triplication followed by loss of a TMS in the APC family, to give the repeat units that are characteristic of these two superfamilies.

Arginine oscillation explains Na + independence in the substrate/product antiporter CaiT

“…Strikingly, the crystal structures revealed that CaiT adopts a fold similar to that of the LeuT-type transporters (7,10,11). This places it in the amino acid-polyamine-organocation (APC) superfamily (12), which shares a conserved architecture of two inverted repeats of five transmembrane (TM) helices each, implying common mechanistic principles. Among the APC transporters, the leucine transporter LeuT from the neurotransmitter/sodium symporter family (10), the betaine transporter BetP from the betaine/choline/ carnitine transporter family (13), the benzyl-hydantoin transporter Mhp1 of the nucleobase/cation symport 1 family, and the Na + / galactose symporter vSGLT of the solute/sodium symporter family are substrate/sodium symporters (14,15).…”

Holins in Bacteria, Eukaryotes, and Archaea: Multifunctional Xenologues with Potential Biotechnological and Biomedical Applications

“…However, one cannot establish independent origin based solely on a lack of sequence similarity because sequence divergence can mask the common features of homologues that arose from a common ancestry (22)(23)(24). In establishing homology, it is imperative to use rigorous statistical methods to identify family and superfamily relationships.…”

The Aspergillus nidulans Proline Permease as a Model for Understanding the Factors Determining Substrate Binding and Specificity of Fungal Amino Acid Transporters

“…The majority of these proteins belong to the ubiquitous amino acid polyamine organocation (APC) 5 superfamily, one of the largest families of secondary transporters (1,2). The APC includes members that function as solute/cation symporters and solute/solute antiporters and are found in bacteria, archeae, fungi, protists, plants and animals (1,3). Fungal APC members belong to the yeast amino acid transporter (YAT) family (4).…”