2.A.75 The L-Lysine Exporter (LysE) Family

Two members of the LysE family (LysE of Corynebacterium glutamicum and ArgO of E. coli) have been functionally characterized, but functionally uncharacterized homologues are encoded within the genomes of many bacteria including Mycobacterium tuberculosis, Bacillus subtilis, Aeromonas salmonicida, Helicobacter pylori, Vibrio cholerae and Yersinia pestis. Thus, LysE family members are found widely distributed in Gram-negative and Gram-positive bacteria. These proteins are 190-240 amino acyl residues in length and possess six hydrophobic regions. PhoA fusion analyses of LysE of C. glutamicum provided evidence for a 5 transmembrane α-helical spanner (TMS) typology with the N-terminus inside and the C-terminus outside (Vrljic et al., 1999). However, some evidence suggests a 6 TMS topology (R. Kramer, personal communication).

LysE appears to catalyze unidirectional efflux of L-lysine (and other basic amino acids such as L-arginine), and it provides the sole route for L-lysine excretion. The energy source is believed to be the proton motive force (H+ antiport). The E. coli ArgO homologue effluxes arginine and possibly lysine and canavanine as well (Nandineni and Gowrishankar, 2004).

Early studies showed that the LysE family is related to the RhtB family (TC #2.A.76) as well as the CadD family (TC #2.A.77) based both on the similar sizes and topologies of their members and on PSI-BLAST results (Vrljic et al., 1999). Thus, three families comprise the LysE superfamily, the members of which are restricted to bacteria and archaea.

The generalized transport reaction for LysE is:

Lysine (in) + [nH+ (out) or nOH- (in)] Lysine (out) + [nH+ (in) or nOH- (out)]



This family belongs to the LysE Superfamily.

 

References:

Aleshin, V.V., N.P. Zakataeva, and V.A. Livshits, (1999). A new family of amino-acid-efflux proteins. Trends Biochem. Sci. 24: 133-135.

Bröer, S. and R. Krämer. (1991a). Lysine excretion by Corrynebacterium glutamicum. 1. Identification of a specific secretion carrier system. Eur. J. Biochem. 202: 131-135.

Bröer, S. and R. Krämer. (1991b). Lysine excretion by Corynebacterium glutamicum. 2. Energetics and mechanism of the transport system. Eur. J. Biochem. 202: 137-143.

Cai, T., W. Cai, J. Zhang, H. Zheng, A.M. Tsou, L. Xiao, Z. Zhong, and J. Zhu. (2009). Host legume-exuded antimetabolites optimize the symbiotic rhizosphere. Mol. Microbiol. 73: 507-517.

Lubitz, D., J.M. Jorge, F. Pérez-García, H. Taniguchi, and V.F. Wendisch. (2016). Roles of export genes cgmA and lysE for the production of L-arginine and L-citrulline by Corynebacterium glutamicum. Appl. Microbiol. Biotechnol. 100: 8465-8474.

Marbaniang, C.N. and J. Gowrishankar. (2012). Transcriptional cross-regulation between Gram-negative and gram-positive bacteria, demonstrated using ArgP-argO of Escherichia coli and LysG-lysE of Corynebacterium glutamicum. J. Bacteriol. 194: 5657-5666.

Nandineni, M.R. and J. Gowrishankar. (2004). Evidence for an arginine exporter encoded by yggA (argO) that is regulated by the LysR-type transcriptional regulator ArgP in Escherichia coli. J. Bacteriol. 186: 3539-3546.

Pathania, A. and A.A. Sardesai. (2015). Distinct Paths for Basic Amino Acid Export in Escherichia coli: YbjE (LysO) Mediates Export of l-Lysine. J. Bacteriol. 197: 2036-2047.

Pathania, A., A.K. Gupta, S. Dubey, B. Gopal, and A.A. Sardesai. (2016). The Topology of the l-Arginine Exporter ArgO Conforms to an Nin-Cout Configuration in Escherichia coli: Requirement for the Cytoplasmic N-Terminal Domain, Functional Helical Interactions, and an Aspartate Pair for ArgO Function. J. Bacteriol. 198: 3186-3199.

Stäbler, N., T. Oikawa, M. Bott, and L. Eggeling. (2011). Corynebacterium glutamicum as a host for synthesis and export of D-Amino Acids. J. Bacteriol. 193: 1702-1709.

Vrljic, M., H. Sahm, and L. Eggeling. (1996). A new type of transporter with a new type of cellular function: L-lysine export from Corynebacterium glutamicum. Mol. Microbiol. 22: 815-826.

Vrljic, M., J. Garg, A. Bellmann, S. Wachi, R. Freudl, M.J. Malecki, H. Sahm, V.J. Kozina, L. Eggeling, and M.H. Saier, Jr. (1999). The LysE superfamily: topology of the lysine exporter LysE of Corynebacterium glutamicum, a paradigm for a novel superfamily of transmembrane solute translocators. J. Mol. Microbiol. Biotechnol. 1: 327-336.

Examples:

TC#NameOrganismal TypeExample
2.A.75.1.1

D- and L-lysine, L-histidine and L-arginine exporter (LysE) (Stäbler et al. 2011).  The system may also export L-citrulline (Lubitz et al. 2016).

Actinobacteria

LysE of Corynebacterium glutamicum

 
2.A.75.1.2

L-arginine exporter (ArgO or YggA) (Nandineni and Gowrishankar 2004).  ArgP-ArgO of E. coli exhibits transcriptional cross activity with the corresponding pair, LysG-LysE of Corynebacterium glutamicum (Marbaniang and Gowrishankar 2012).  ArgO when overproducted confers sensitivity to the toxic arginine analogue, canavanine and catalyzes export of L-lysine (Pathania and Sardesai 2015). ArgO assumes an Nin-Cout configuration, potentially forming a five-transmembrane helix bundle flanked by a cytoplasmic N-terminal domain (NTD) comprising roughly its first 38 to 43 amino acyl residues and a short periplasmic C-terminal region (CTR). Mutagenesis studies indicate that the CTR, but not the NTD, is dispensable for ArgO function in vivo, and that a pair of conserved aspartate residues, located near the opposing edges of the cytoplasmic membrane, may play a pivotal role in facilitating transmembrane Arg flux (Pathania et al. 2016). ArgO possesses a membrane topology that is distinct from that reported for LysE, with substantial variation in the topological arrangement of the proximal one-third portions of the two exporters. The Arg-translocating conduit is formed by a monomer of ArgO (Pathania et al. 2016).

Proteobacteria

ArgO (YggA) of E. coli

 
2.A.75.1.3Putative amino-acid transporter Rv0488/MT0507BacteriaRv0488 of Mycobacterium tuberculosis
 
2.A.75.1.4

Canavanine exporter of 202 aas and 6 TMSs, MsiA, promoting canavanine resistance (Cai et al. 2009).  Canavanine is a plant product present in seeds and plant exudates. 

Proteobacteria

MsiA of Mesorhizobium tianshanense