6gs5

From Proteopedia

(Difference between revisions)

Current revision

NMR structure of temporin L in SDS micelles

Structural highlights

6gs5 is a 1 chain structure with sequence from Rana temporaria. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	Solution NMR
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

TPL_RANTE Amphipathic alpha-helical antimicrobial peptide with potent activity against both Gram-negative and Gram-positive bacteria, and against fungi (PubMed:12133008, PubMed:16867990, PubMed:18370376, PubMed:31358802, PubMed:9022710). 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 (Probable) (PubMed:16801429). 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]

Publication Abstract from PubMed

Frogs such as Rana temporaria and Litoria aurea secrete numerous closely related antimicrobial peptides (AMPs) as an effective chemical dermal defence. Damage or penetration of the bacterial plasma membrane is considered essential for AMP activity and such properties are commonly ascribed to their ability to form secondary amphipathic, alpha-helix conformations in membrane mimicking milieu. Nevertheless, despite the high similarity in physical properties and preference for adopting such conformations, the spectrum of activity and potency of AMPs often varies considerably. Hence distinguishing apparently similar AMPs according to their behaviour in, and effects on, model membranes will inform understanding of primary-sequence-specific antimicrobial mechanisms. Here we use a combination of molecular dynamics simulations, circular dichroism and patch-clamp to investigate the basis for differing anti-bacterial activities in representative AMPs from each species; temporin L and aurein 2.5. Despite adopting near identical, alpha-helix conformations in the steady-state in a variety of membrane models, these two AMPs can be distinguished both in vitro and in silico based on their dynamic interactions with model membranes, notably their differing conformational flexibility at the N-terminus, ability to form higher order aggregates and the characteristics of induced ion conductance. Taken together, these differences provide an explanation of the greater potency and broader antibacterial spectrum of activity of temporin L over aurein 2.5. Consequently, while the secondary amphipathic, alpha-helix conformation is a key determinant of the ability of a cationic AMP to penetrate and disrupt the bacterial plasma membrane, the exact mechanism, potency and spectrum of activity is determined by precise structural and dynamic contributions from specific residues in each AMP sequence.

Temporin L and aurein 2.5 have identical conformations but subtly distinct membrane and antibacterial activities.,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 Sci Rep. 2019 Jul 29;9(1):10934. doi: 10.1038/s41598-019-47327-w. PMID:31358802^[9]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ 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
↑ 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
↑ 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
↑ 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
↑ 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
↑ 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
↑ 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
↑ 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
↑ 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

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/6gs5"

Categories: Large Structures | Rana temporaria | Manzo G | Mason JA

@@ Line 4: / Line 4: @@
 == Structural highlights ==
 <table><tr><td colspan='2'>[[6gs5]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Rana_temporaria Rana temporaria]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6GS5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6GS5 FirstGlance]. <br>
-</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6gs5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6gs5 OCA], [https://pdbe.org/6gs5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6gs5 RCSB], [https://www.ebi.ac.uk/pdbsum/6gs5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6gs5 ProSAT]</span></td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6gs5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6gs5 OCA], [https://pdbe.org/6gs5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6gs5 RCSB], [https://www.ebi.ac.uk/pdbsum/6gs5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6gs5 ProSAT]</span></td></tr>
 </table>
 == Function ==
-[https://www.uniprot.org/uniprot/TPL_RANTE 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]<ref>PMID:12133008</ref> <ref>PMID:16801429</ref> <ref>PMID:16867990</ref> <ref>PMID:18370376</ref> <ref>PMID:21586570</ref> <ref>PMID:31358802</ref> <ref>PMID:9022710</ref> <ref>PMID:21586570</ref>
+[https://www.uniprot.org/uniprot/TPL_RANTE TPL_RANTE] Amphipathic alpha-helical antimicrobial peptide with potent activity against both Gram-negative and Gram-positive bacteria, and against fungi (PubMed:12133008, PubMed:16867990, PubMed:18370376, PubMed:31358802, PubMed:9022710). 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 (Probable) (PubMed:16801429). 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]<ref>PMID:12133008</ref> <ref>PMID:16801429</ref> <ref>PMID:16867990</ref> <ref>PMID:18370376</ref> <ref>PMID:21586570</ref> <ref>PMID:31358802</ref> <ref>PMID:9022710</ref> <ref>PMID:21586570</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==

6gs5

From Proteopedia

Current revision

NMR structure of temporin L in SDS micelles

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

Personal tools

Navigation

Search

Toolbox