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 2.A.86 The Autoinducer-2 Exporter (AI-2E) Family (formerly the PerM Family, TC #9.B.22)

  The AI-2E family (UPF0118) is a large family of prokaryotic proteins derived from a variety of bacteria and archaea. Those examined are about 350 residues in length, and the couple that have been examined exhibit 7 putative TMSs (Rettner and Saier, 2010). E. coli, B. subtilis and several other prokaryotes have multiple paralogues encoded within their genomes. Herzberg et al. (2006) have presented strong evidence for a role of a AI-2E family homologue, YdgG (renamed TqsA) is an exporter of the E. coli autoinducer-2 (AI-2) (Camilli and Bassler, 2006; Chen et al., 2002). AT-2 is a proposed signalling molecule for interspecies communication in bacteria. It is a furanosyl borate diester (Chen et al., 2002). It is induced in Bacillus subtilis by exposure to rice seedlings (Xie et al. 2015).  AI-2, a universal molecule for both intra- and inter-species communication, is involved in the regulation of biofilm formation, virulence, motility, chemotaxis, and antibiotic resistance. (Khera et al. 2022).
   More recently, it has been reported that this family includes a member of the
UPF0118 family (which was the former designation for the AI-2E family), and this transmembrane protein with 7 TMSs, exhibits reversible pH-dependent Na+ or Li+/H+ antiport activity. Phylogenetic analyses were reported (Dong et al. 2017).  Thus, it appears that different members of the family may have very different transport functions. Cryo-EM structures of two pentameric autoinducer-2 exporter from E. coli (TqsA (TC# 2.A.86.1.4) and YdiK (TC# 2.A.86.2.1) revealed the probable transport mechanism (Khera et al. 2022). Each of the 5 subunits is believed to be a functional unit, and an elevator-type mechanism has been suggested.


The transport reactions catalyzed by membeers of the AI-2E family are:

AI-2 (in) ⇌ AI-2 (out)

Na+ or Li+ (out) + H+ (in) → Na+ or Li+ (in) + H+ (out)

References associated with 2.A.86 family:

Besse A., Peduzzi J., Rebuffat S. and Carre-Mlouka A. (2015). Antimicrobial peptides and proteins in the face of extremes: Lessons from archaeocins. Biochimie. 118:344-55. 26092421
Camilli, A. and Bassler, B.L. (2006). Bacterial small-molecule signaling pathways. Science 311: 1113-1116. 16497924
Chen, X., S. Schauder, N. Potier, A. Van Dorsselaer, I. Pelczer, B.L. Bassler, and F.M. Hughson. (2002). Structural identification of a bacterial quorum-sensing signal containing boron. Nature 415: 488-489. 11823863
Dong, P., L. Wang, N. Song, L. Yang, J. Chen, M. Yan, H. Chen, R. Zhang, J. Li, H. Abdel-Motaal, and J. Jiang. (2017). A UPF0118 family protein with uncharacterized function from the moderate halophile Halobacillus andaensis represents a novel class of Na(Li)/H antiporter. Sci Rep 7: 45936. 28374790
Eichenberger, P., S.T. Jensen, E.M. Conlon, C. van Ooij, J. Silvaggi, J.E. González-Pastor, M. Fujita, S. Ben-Yehuda, P. Stragier, J.S. Liu, and R. Losick. (2003). The sigmaE regulon and the identification of additional sporulation genes in Bacillus subtilis. J. Mol. Biol. 327: 945-972. 12662922
Herzberg, M., I.K. Kaye, W. Peti, and T.K. Wood. (2006). YdgG (TqsA) controls biofilm formation in Escherichia coli K-12 through autoinducer 2 transport. J. Bacteriol. 188: 587-598. 16385049
Khera, R., A.R. Mehdipour, J.R. Bolla, J. Kahnt, S. Welsch, U. Ermler, C. Muenke, C.V. Robinson, G. Hummer, H. Xie, and H. Michel. (2022). Cryo-EM structures of pentameric autoinducer-2 exporter from Escherichia coli reveal its transport mechanism. EMBO. J. e109990. [Epub: Ahead of Print] 35698912
Kociolek, L.K., D.N. Gerding, D.W. Hecht, and E.A. Ozer. (2018). Comparative genomics analysis of Clostridium difficile epidemic strain DH/NAP11/106. Microbes Infect 20: 245-253. 29391259
Nobre, L.S., F. Al-Shahrour, J. Dopazo, and L.M. Saraiva. (2009). Exploring the antimicrobial action of a carbon monoxide-releasing compound through whole-genome transcription profiling of Escherichia coli. Microbiology 155: 813-824. 19246752
Poppleton, D.I., M. Duchateau, V. Hourdel, M. Matondo, J. Flechsler, A. Klingl, C. Beloin, and S. Gribaldo. (2017). Outer Membrane Proteome of A Diderm Firmicute of the Human Microbiome. Front Microbiol 8: 1215. 28713344
Ravcheev, D.A., M.S. Gel'fand, A.A. Mironov, and A.B. Rakhmaninova. (2002). [Purine regulon of γ-proteobacteria: a detailed description]. Genetika 38: 1203-1214. 12391881
Rettner, R.E. and M.H. Saier, Jr. (2010). The autoinducer-2 exporter superfamily. J. Mol. Microbiol. Biotechnol. 18: 195-205. 20559013
Shao, L., T. Xu, X. Zheng, D. Shao, H. Zhang, H. Chen, Z. Zhang, M. Yan, H. Abdel-Motaal, and J. Jiang. (2020). A novel three-TMH Na/H antiporter and the functional role of its oligomerization. J. Mol. Biol. 433: 166730. [Epub: Ahead of Print] 33279580
Turner, M.S. and J.D. Helmann. (2000). Mutations in multidrug efflux homologs, sugar isomerases, and antimicrobial biosynthesis genes differentially elevate activity of the σX and σW factors in Bacillus subtilis. J. Bacteriol. 182: 5202-5210. 10960106
Xie, S., H. Wu, L. Chen, H. Zang, Y. Xie, and X. Gao. (2015). Transcriptome profiling of Bacillus subtilis OKB105 in response to rice seedlings. BMC Microbiol 15: 21. 25651892