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2.A.56 The Tripartite ATP-independent Periplasmic Transporter (TRAP-T) Family

TRAP-T family permeases generally consist of three components, and these systems have so far been found in Gram-negative bacteria, Gram-positive bacteria and archaea. Several members of the family have been both sequenced and functionally characterized. The first system to be characterized was the DctPQM system of Rhodobacter capsulatus (Forward et al., 1997), and it is the prototype for the TRAP-T family (Kelly and Thomas, 2001; Rabus et al., 1999).

DctP is a periplasmic dicarboxylate (malate, fumarate, succinate) binding receptor that is biochemically well-characterized. The 3-dimensional structure of a homologue, SiaTP (TC #2.A.56.1.3) has been solved (Muller et al., 2006). DctQ is an integral cytoplasmic membrane protein (25 kDa) with 4 putative transmembrane α-helical spanners (TMSs). DctM is a second integral cytoplasmic membrane protein (50 kDa) with 12 putative TMSs. These three proteins have been shown to be both necessary and sufficient for the proton motive force-dependent uptake of dicarboxylates into R. capsulatus. An involvement of ATP in transport energization was excluded.  The substrate-binding protein, SiaP, imposes directionality on an electrochemical sodium gradient-driven TRAP transporter, SiaPQM (Mulligan et al., 2009).

In several TRAP-T systems, fused Q-M-type proteins instead of two separate Q- and M-type proteins are found, while in others, Q-P-type fusion proteins are found. The operon encoding the Synechocystis system includes a protein homologous to the glutamine binding protein, and biochemical evidence has suggested that a glutamate transporter from Rhodobacter sphaeroides is a periplasmic binding protein-dependent, pmf-dependent secondary carrier (Jacobs et al., 1996). Homologous systems in Halomonas elongata and Rhodobacter spheroides take up ectoine/hydroxyectoine and taurine, respectively (Bruggemann et al., 2004; Grammann et al., 2002). The DctP dicarboxylate receptor is homologous to both the YiaO monocarboxylate receptor and the TeaA ectoine receptor. Thus, the TRAP-T family of permeases may be involved in the uptake of widely divergent compounds, mostly carboxylate derivatives (Kelly and Thomas, 2001; Thomas et al., 2006; Mulligan et al., 2007).

The crystal structure of SiaP (the receptor for SiaTP; TC #2.A.56.1.3) reveals an overall topology similar to ATP binding cassette receptors, which is not apparent from the sequence, demonstrating that primary and secondary transporters can share a common structural component (Müller et al., 2006). The structure of SiaP in the presence of the sialic acid analogue 2,3-didehydro-2-deoxy-N-acetylneuraminic acid reveals the ligand bound in a deep cavity with its carboxylate group forming a salt bridge with a highly conserved Arg residue. Sialic acid binding, which obeys simple bimolecular association kinetics, is accompanied by domain closure about a hinge region and the kinking of an α-helix hinge component. The structure provides insight into the evolution, mechanism, and substrate specificity of TRAP-transporters (Müller et al., 2006).

The solute binding receptor, DctP, has a structure comprised of two domains connected by a hinge that closes upon substrate binding, similar to those in ABC uptake porters. Substrate binding is mediated through a conserved and specific arginine/carboxylate interaction in the receptor. Mulligan et al. (2011) have reviewed the expanding repertoire of substrates and physiological roles for experimentally characterized TRAP transporters in bacteria and discuss mechanistic aspects. TRAP transporters are high-affinity, Na+-dependent unidirectional secondary transporters.

A subfamily of TRAP-Ts [tetratricopeptide repeat-protein associated TRAP transporters (TPATs)] has four components. Three are common to both TRAP-Ts and TPATs. TPATs are distinguished from TRAP-Ts by the presence of a protein called the 'T component'. In Treponema pallidum, this protein (TatT) is a water-soluble trimer whose protomers are each perforated by a pore. Its respective P component (TatP(T)) interacts with TatT. Co-crystal structures of two complexes showed that up to three monomers of TatP(T) can bind to the TatT trimer. A putative ligand-binding cleft of TatP(T) aligns with the pore of TatT, strongly suggesting ligand transfer between T and P(T) (Brautigam et al., 2012).

The generalized transport reaction presumed to be catalyzed by TRAP-T family permeases is:

solute (out) + nH+ (out) → solute (in) + nH+ (in).

 

References associated with 2.A.56 family:

Allen, S., A. Zaleski, J.W. Johnston, B.W. Gibson, M.A. Apicella. (2005). Novel sialic acid transporter of Haemophilus influenzae. Infect. Immun. 73: 5291-5300. 16113244
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Bruggemann, C., K. Denger, A.M. Cook, and J. Ruff. (2004 ). Enzymes and genes of taurine and isethionate dissimilation in Paracoccus denitrificans. Microbiology 150: 805-816. 15073291
Chae, J.C. and G.J. Zylstra. (2006). 4-Chlorobenzoate uptake in Comamonas sp. strain DJ-12 is mediated by a tripartite ATP-independent periplasmic transporter. J. Bacteriol. 188: 8407-8412. 17041053
Chen, A.M., Y.B. Wang, S. Jie, A.Y. Yu, L. Luo, G.Q. Yu, J.B. Zhu, and Y.Z. Wang. (2010). Identification of a TRAP transporter for malonate transport and its expression regulated by GtrA from Sinorhizobium meliloti. Res. Microbiol. 161: 556-564. 20594941
Deka, R.K., C.A. Brautigam, M. Goldberg, P. Schuck, D.R. Tomchick, and M.V. Norgard. (2012). Structural, Bioinformatic, and In Vivo Analyses of Two Treponema pallidum Lipoproteins Reveal a Unique TRAP Transporter. J. Mol. Biol. 416: 678-696. 22306465
Denger, K., T.H. Smits, and A.M. Cook. (2006). Genome-enabled analysis of the utilization of taurine as sole source of carbon or of nitrogen by Rhodobacter sphaeroides 2.4.1. Microbiology 152: 3197-3206. 17074891
Forward, J., M.C. Behrendt, N.R. Wyborn, R. Cross, and D.J. Kelly. (1997). TRAP Transporters: a new family of periplasmic solute transport systems encoded by the dctPQM genes of Rhodobacter capsulatus and by homologs in diverse Gram-negative bacteria. J. Bacteriol. 179: 5482-5493. 9287004
Grammann, K., A. Volke, and H.J. Kunte. (2002). New type of osmoregulated solute transporter identified in halophilic members of the Bacteria domain: TRAP transporter TeaABC mediates uptake of ectoine and hydroxyectoine in Halomonas elongata DSM 2581T. J. Bacteriol. 184: 3078-3085. 12003950
Hopkins, A.P., J.A. Hawkhead, and G.H. Thomas. (2013). Transport and catabolism of the sialic acids N-glycolylneuraminic acid and 3-keto-3-deoxy-d-glycero-d-galactonononic acid by Escherichia coli K-12. FEMS Microbiol. Lett. [Epub: Ahead of Print] 23848303
Jacobs, M.H.J., T. van der Heide, A.J.M. Driessen, and W.N. Konings. (1996). Glutamate transport in Rhodobacter sphaeroides is mediated by a novel binding-protein dependent secondary transport system. Proc. Natl. Acad. Sci. USA 93: 12786-12790. 8917497
Johnston, J.W., N.P. Coussens, S. Allen, J.C. Houtman, K.H. Turner, A. Zaleski, S. Ramaswamy, B.W. Gibson, and M.A. Apicella. (2008). Characterization of the N-acetyl-5-neuraminic acid-binding site of the extracytoplasmic solute receptor (SiaP) of nontypeable Haemophilus influenzae strain 2019. J. Biol. Chem. 283(2): 855-865. 17947229
Kelly, D.J. and G.H. Thomas. (2001). The tripartite ATP-independent periplasmic (TRAP) transporters of bacteria and archaea. FEMS Microbiol. Rev. 25: 405-424. 11524131
Lee, M., S.G. Woo, G. Park, and M.K. Kim. (2011). Paracoccus caeni sp. nov., isolated from sludge. Int J Syst Evol Microbiol 61: 1968-1972. 20851920
Mulligan, C., A.P. Leech, D.J. Kelly, and G.H. Thomas. (2012). The membrane proteins SiaQ and SiaM form an essential stoichiometric complex in the sialic acid tripartite ATP-independent periplasmic (TRAP) transporter SiaPQM (VC1777-1779) from Vibrio cholerae. J. Biol. Chem. 287: 3598-3608. 22167185
Mulligan, C., D.J. Kelly, and G.H. Thomas. (2007). Tripartite ATP-independent periplasmic (TRAP) transporters: application of a relational database (TRAPDb) for genome-wide analysis of transporter gene frequency and organization. J. Mol. Microbiol. Biotechnol. (in press). 17587870
Mulligan, C., E.R. Geertsma, E. Severi, D.J. Kelly, B. Poolman, and G.H. Thomas. (2009). The substrate-binding protein imposes directionality on an electrochemical sodium gradient-driven TRAP transporter. Proc. Natl. Acad. Sci. USA 106: 1778-1783. 19179287
Mulligan, C., M. Fischer, and G.H. Thomas. (2011). Tripartite ATP-independent periplasmic (TRAP) transporters in bacteria and archaea. FEMS Microbiol. Rev. 35: 68-86. 20584082
Müller, A., E. Severi, C. Mulligan, A.G. Watts, D.J. Kelly, K.S. Wilsonz, A.J. Wilkinson, and G.H. Thomas. (2006). Conservation of structure and mechanism in primary and secondary transporters exemplified by SiaP, a sialic acid binding virulence factor from Haemophilus influenzae. J. Biol. Chem. 281: 22212-22222. 16702222
Pernil, R., A. Herrero, and E. Flores. (2010). A TRAP transporter for pyruvate and other monocarboxylate 2-oxoacids in the cyanobacterium Anabaena sp. strain PCC 7120. J. Bacteriol. 192: 6089-6092. 20851902
Quintero, M.J., M.L. Montesinos, A. Herrero, and E. Flores. (2001). Identification of genes encoding amino acid permeases by inactivation of selected ORFs from the Synechocystis genomic sequence. Genome Res. 11: 2034-2040. 11731493
Rabus, R., D.L. Jack, D.J. Kelly, and M.H. Saier, Jr. (1999). TRAP transporters: an ancient family of extracytoplasmic solute-receptor-dependent secondary active transporters. Microbiology 145: 3431-3445. 10627041
Rodionov, D.A., M.S. Gelfand, and N. Hugouvieux-Cotte-Pattat. (2004). Comparative genomics of the KdgR regulon in Erwinia chrysanthemi 3937 and other γ-proteobacteria. Microbiology 150: 3571-3590. 15528647
Rodionov, D.A., P. Hebbeln, A. Eudes, J. ter Beek, I.A. Rodionova, G.B. Erkens, D.J. Slotboom, M.S. Gelfand, A.L. Osterman, A.D. Hanson, and T. Eitinger. (2009). A novel class of modular transporters for vitamins in prokaryotes. J. Bacteriol. 191: 42-51. 18931129
Severi, E., G. Randle, P. Kivlin, K. Whitfield, R. Young, R. Moxon, D. Kelly, D. Hood, and G.H. Thomas. (2005). Sialic acid transport in Haemophilus influenzae is essential for lipopolysaccharide sialylation and serum resistance and is dependent on a novel tripartite ATP-independent periplasmic transporter. Mol. Microbiol. 58: 1173-1185. 16262798
Thomas, G.H., T. Southworth, M.R. León-Kempis, A. Leech, and D.J. Kelly. (2006). Novel ligands for the extracellular solute receptors of two bacterial TRAP transporters. Microbiology 152: 187-198. 16385129