2maa
From Proteopedia
NMR structure of Temporin-1 Ta in lipopolysaccharide micelles: Mechanistic insight into inactivation by outer memebrane
Structural highlights
FunctionTPA_RANTE Amphipathic alpha-helical antimicrobial peptide with potent activity against Gram-positive bacteria, weak activity against Gram-negative bacteria, and moderate activity against fungi (PubMed:9022710, PubMed:15513914, PubMed:16867990, PubMed:18255189, PubMed:18370376). Mainly acts by causing membrane permeabilization (Probable). Is also able to kill S.aureus (both wild-type and MRSA) that are internalized in human keratinocytes without injuring host cells (PubMed:24514087). Rapidly inactivates both channel catfish herpesvirus (ED(50)=15 uM) and frog virus 3 (ED(50)=58 uM) over a wide temperature range (PubMed:15193922). Also displays anti-leishmania activity by damaging parasite membrane (PubMed:15513914, PubMed:25668079). Acts synergistically with temporin-L which improves temporin-1Ta activity by preventing its self-association in lipopolysaccharides (LPS) (PubMed:16867990). Does not show hemolytic activity (PubMed:15513914). In vitro, stimulates insulin release from pancreatic beta-cells in a dose-dependent manner without increasing intracellular calcium, protects beta-cells against cytokine-induced apoptosis and augments beta-cells proliferation (PubMed:29349894). In vivo, intraperitoneal injection together with a glucose load into mice does not have effect on plasma glucose levels (PubMed:29349894). In vivo, when tested on mice with methicillin-resistant S.aureus (MRSA)-infected wounds, this peptide inhibits bacterial growth and shows wound healing effect (PubMed:18255189). In vitro, promotes cell migration and wound healing (PubMed:24514087).[1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [11] Publication Abstract from PubMedBACKGROUND: Antimicrobial peptides (AMPs) play important roles in the innate defense mechanism. The broad spectrum of activity of AMPs requires an efficient permeabilization of the bacterial outer and inner membranes. The outer leaflet of the outer membrane of Gram negative bacteria is made of a specialized lipid called lipopolysaccharide (LPS). The LPS layer is an efficient permeability barrier against anti-bacterial agents including AMPs. As a mode of protection, LPS can induce self associations of AMPs rendering them inactive. Temporins are a group of short-sized AMPs isolated from frog skin, and many of them are inactive against Gram negative bacteria as a result of their self-association in the LPS-outer membrane. PRINCIPAL FINDINGS: Using NMR spectroscopy, we have determined atomic resolution structure and characterized localization of temporin-1Ta or TA (FLPLIGRVLSGIL-amide) in LPS micelles. In LPS micelles, TA adopts helical conformation for residues L4-I12, while residues F1-L3 are found to be in extended conformations. The aromatic sidechain of residue F1 is involved in extensive packing interactions with the sidechains of residues P3, L4 and I5. Interestingly, a number of long-range NOE contacts have been detected between the N-terminal residues F1, P3 with the C-terminal residues S10, I12, L13 of TA in LPS micelles. Saturation transfer difference (STD) NMR studies demonstrate close proximity of residues including F1, L2, P3, R7, S10 and L13 with the LPS micelles. Notably, the LPS bound structure of TA shows differences with the structures of TA determined in DPC and SDS detergent micelles. SIGNIFICANCE: We propose that TA, in LPS lipids, forms helical oligomeric structures employing N- and C-termini residues. Such oligomeric structures may not be translocated across the outer membrane; resulting in the inactivation of the AMP. Importantly, the results of our studies will be useful for the development of antimicrobial agents with a broader spectrum of activity. NMR structure of temporin-1 ta in lipopolysaccharide micelles: mechanistic insight into inactivation by outer membrane.,Saravanan R, Joshi M, Mohanram H, Bhunia A, Mangoni ML, Bhattacharjya S PLoS One. 2013 Sep 9;8(9):e72718. doi: 10.1371/journal.pone.0072718. eCollection , 2013. PMID:24039798[12] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. Loading citation details.. Citations No citations found References
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