Extra domains in secondary transport carriers and channel proteins

Abstract

"Extra" domains in members of the families of secondary transport carrier and channel proteins provide secondary functions that expand, amplify or restrict the functional nature of these proteins. Domains in secondary carriers include TrkA and SPX domains in DASS family members, DedA domains in TRAP-T family members (both of the IT superfamily), Kazal-2 and PDZ domains in OAT family members (of the MF superfamily), USP, IIA(Fru) and TrkA domains in ABT family members (of the APC superfamily), ricin domains in OST family members, and TrkA domains in AAE family members. Some transporters contain highly hydrophilic domains consisting of multiple repeat units that can also be found in proteins of dissimilar function. Similarly, transmembrane alpha-helical channel-forming proteins contain unique, conserved, hydrophilic domains, most of which are not found in carriers. In some cases the functions of these domains are known. They may be ligand binding domains, phosphorylation domains, signal transduction domains, protein/protein interaction domains or complex carbohydrate-binding domains. These domains mediate regulation, subunit interactions, or subcellular targeting. Phylogenetic analyses show that while some of these domains are restricted to closely related proteins derived from specific organismal types, others are nearly ubiquitous within a particular family of transporters and occur in a tremendous diversity of organisms. The former probably became associated with the transporters late in the evolutionary process; the latter probably became associated with the carriers much earlier. These domains can be located at either end of the transporter or in a central region, depending on the domain and transporter family. These studies provide useful information about the evolution of extra domains in channels and secondary carriers and provide novel clues concerning function.

Topology of AspT, the Aspartate:Alanine Antiporter of Tetragenococcus halophilus , Determined by Site-Directed Fluorescence Labeling

“…The topology analyses revealed that AspT does indeed have a unique topology; the protein has 10 TMs, a large hydrophilic cytoplasmic loop (about 180 amino acids) between TM5 and TM6, and N and C termini that face the periplasm. Computations using recent genome data have predicted that the AAE family is composed of membrane proteins possessing a unique membrane topology (11), and our topology analyses support this prediction.…”

“…We found 90 aspT orthologues, such as yidE and ybjL of E. coli, in 60 bacterial or archaebacterial genomes (20) (11) found in the regulatory subunit TrkA of the bacterial potassium uptake system (9).…”

“…Recently, the results of a BLAST (http://www.ncbi.nlm.nih .gov/BLAST/ [5]) search of the nucleotide sequence of the aspT gene and the amino acid sequence of the AspT protein against current nucleotide and protein databases have suggested that AAE family transporters are conserved in many bacterial species (11,20). AspT is the only functionally characterized protein belonging to the AAE family (2).…”

Studying membrane proteins through the eyes of the genetic code revealed a strong uracil bias in their coding mRNAs

“…Interestingly, the differences between multipass membrane proteins and cytoplasmic proteins seem to decrease through evolution, both regarding the hydrophobicity and U-richness, in a manner that fits the phylogenetic tree of life according to Carl Woese (18). One possible contribution to this tendency would be that membrane proteins have acquired more soluble domains through evolution (19,20), thus reducing the overall proteins' hydrophobicities and the U-richness of their encoding mRNAs. This development complicates examining possible (predicted) effects of the genome GC content on the U bias.…”

Substrate Specificity of the Aspartate:Alanine Antiporter (AspT) of Tetragenococcus halophilus in Reconstituted Liposomes

“…AspT is classified as a conventional secondary transport protein and belongs to the newly classified aspartate:alanine exchanger family (TC number 2.A.81) of transporters in the system developed by Saier et al (25,26). Recently, the results of a BLAST (7) search of the nucleotide sequence of the aspT gene and the amino acid sequence of the AspT protein against current nucleotide and protein data bases, respectively, suggested that the aspartate:alanine exchanger transporters are conserved in many bacterial species (8,9). Very recently, Fukui et al (10) found SucE1, an aspartate:alanine exchanger transporter from Corynebacterium glutamicum, plays a role in the export of succinate generated during fermentation.…”