TCDB is operated by the Saier Lab Bioinformatics Group

9.B.40 The DotA/TraY (DotA/TraY) Family

The DotA protein of Legionella pneumophila is a polytopic membrane protein with 1048 aas and 13 putative TMSs. Its topology looks superficially like an RND permease with two integral membrane domains of about 6 TMSs each separated by a large hydrophilic domain. This protein is homologous to TraY of plasmid R64 (745 aas; BAA78013) as well as a protein from Xanthomonas axonopodis (723 aas; AAM37270) (Komano et al., 2000). The latter two proteins are homologous to each other throughout their lengths. They exhibit two hydrophobic domains separated by a large hydrophilic domain as does DotA. Only the transmembrane regions of all three proteins are demonstrably homologous. The hydrophilic region of the Xanthomonas protein shows sequence similarity to prophage Pil protein 46, a large tail fiber host specificity protein of 1441 aas (AAK08401) and to a protein from Listeria innocua of 1066 aas (CAC96422) that is a member of the RND superfamily (most similar to TC #2.A.6.5.1).

DotA is essential for pathogenicity, for replication in macrophages and is secreted from L. pneumophilia via the dot/icm type IV secretion system into the culture fluid (Nagai and Roy, 2001). The first TMS is cleaved off, and the protein forms a pentameric or hexameric hollow ring structure where DotA and another protein of 48 kDa are present in equistoichiometric amounts. Nagai and Roy (2001) propose that DotA forms a pore that becomes inserted into the plasma membrane of the target host cell, allowing type IV protein secretion across the membrane. However, the association of DotA with the host cell membrane has not been demonstrated.

L. pneumophila is an intracellular pathogen that multiplies in a specialized vacuole, the biogenesis of which depends on the Dot/Icm type IV protein translocation system. This complex system can transport target proteins between two bacterial cells (Luo and Isberg, 2004) as well as across the host phagosomal membrane. Many protein substrates of the Dot/Ics system have been identified (Luo and Isberg, 2004).

References associated with 9.B.40 family:

Bumbaugh, A.C., E.A. McGraw, K.L. Page, R.K. Selander, and T.S. Whittam. (2002). Sequence polymorphism of dotA and mip alleles mediating invasion and intracellular replication of Legionella pneumophila. Curr. Microbiol. 44: 314-322. 11927981
Komano, T., T. Yoshida, K. Narahara, and N. Furuya. (2000). The transfer region of IncI1 plasmid R64: similarities between R64 tra and Legionella icm/dot genes. Mol. Microbiol. 35: 1348-1359. 10760136
Luo, Z.Q., and R.R. Isberg. (2004). Multiple substrates of the Legionella pneumophila Dot/Icm system identified by interbacterial protein transfer. Proc. Natl. Acad. Sci. USA 101: 841-846. 14715899
Nagai, H., and C.R. Roy. (2001). The DotA protein from Legionella pneumophila is secreted by a novel process that requires the Dot/Icm transporter. EMBO. J. 20: 5962-5970. 11689436