8tv4

Structural highlights

Function

TPL_RANTE Amphipathic alpha-helical antimicrobial peptide with potent activity against both Gram-negative and Gram-positive bacteria, and against fungi (PubMed:9022710, PubMed:12133008, PubMed:16867990, PubMed:18370376, PubMed:31358802). Mainly acts by causing perturbation of bilayer integrity of both neutral and negatively charged membranes, probably by forming pore-like openings (PubMed:12133008, PubMed:31358802). Also displays anti-leishmania activity by damaging parasite membrane (By similarity). Shows hemolytic activity (PubMed:12133008). Also shows cytotoxicity against cancer cell lines (PubMed:12133008). Strongly binds to lipopolysaccharides (LPS) and its lipid A portion (PubMed:16801429) (Probable). Improves temporin-A and temporin-B activities by preventing their homo-oligomerization in LPS (PubMed:16867990, PubMed:21586570). In vivo, its simultaneous administration with beta-lactam antibiotics produces the highest antimicrobial activities and the strongest reduction in plasma LPS and TNF-alpha levels, resulting in the highest survival rates in rat models of septic shock (PubMed:16801429).[UniProtKB:P56917][UniProtKB:P79874]^{[1] [2] [3] [4] [5] [6] [7] [8]}

References

1. ↑ Rinaldi AC, Mangoni ML, Rufo A, Luzi C, Barra D, Zhao H, Kinnunen PK, Bozzi A, Di Giulio A, Simmaco M. Temporin L: antimicrobial, haemolytic and cytotoxic activities, and effects on membrane permeabilization in lipid vesicles. Biochem J. 2002 Nov 15;368(Pt 1):91-100. PMID:12133008 doi:10.1042/BJ20020806
2. ↑ Giacometti A, Cirioni O, Ghiselli R, Mocchegiani F, Orlando F, Silvestri C, Bozzi A, Di Giulio A, Luzi C, Mangoni ML, Barra D, Saba V, Scalise G, Rinaldi AC. Interaction of antimicrobial peptide temporin L with lipopolysaccharide in vitro and in experimental rat models of septic shock caused by gram-negative bacteria. Antimicrob Agents Chemother. 2006 Jul;50(7):2478-86. PMID:16801429 doi:10.1128/AAC.01553-05
3. ↑ Rosenfeld Y, Barra D, Simmaco M, Shai Y, Mangoni ML. A synergism between temporins toward Gram-negative bacteria overcomes resistance imposed by the lipopolysaccharide protective layer. J Biol Chem. 2006 Sep 29;281(39):28565-74. PMID:16867990 doi:10.1074/jbc.M606031200
4. ↑ Carotenuto A, Malfi S, Saviello MR, Campiglia P, Gomez-Monterrey I, Mangoni ML, Gaddi LM, Novellino E, Grieco P. A different molecular mechanism underlying antimicrobial and hemolytic actions of temporins A and L. J Med Chem. 2008 Apr 24;51(8):2354-62. PMID:18370376 doi:10.1021/jm701604t
5. ↑ Bhunia A, Saravanan R, Mohanram H, Mangoni ML, Bhattacharjya S. NMR structures and interactions of temporin-1Tl and temporin-1Tb with lipopolysaccharide micelles: mechanistic insights into outer membrane permeabilization and synergistic activity. J Biol Chem. 2011 Jul 8;286(27):24394-406. PMID:21586570 doi:10.1074/jbc.M110.189662
6. ↑ Manzo G, Ferguson PM, Hind CK, Clifford M, Gustilo VB, Ali H, Bansal SS, Bui TT, Drake AF, Atkinson RA, Sutton JM, Lorenz CD, Phoenix DA, Mason AJ. Temporin L and aurein 2.5 have identical conformations but subtly distinct membrane and antibacterial activities. Sci Rep. 2019 Jul 29;9(1):10934. doi: 10.1038/s41598-019-47327-w. PMID:31358802 doi:http://dx.doi.org/10.1038/s41598-019-47327-w
7. ↑ Simmaco M, Mignogna G, Canofeni S, Miele R, Mangoni ML, Barra D. Temporins, antimicrobial peptides from the European red frog Rana temporaria. Eur J Biochem. 1996 Dec 15;242(3):788-92. PMID:9022710 doi:10.1111/j.1432-1033.1996.0788r.x
8. ↑ Bhunia A, Saravanan R, Mohanram H, Mangoni ML, Bhattacharjya S. NMR structures and interactions of temporin-1Tl and temporin-1Tb with lipopolysaccharide micelles: mechanistic insights into outer membrane permeabilization and synergistic activity. J Biol Chem. 2011 Jul 8;286(27):24394-406. PMID:21586570 doi:10.1074/jbc.M110.189662