Effect of disulfide bridges deletion on the conformation of the androctonin,polyphemusin-I,and thanatin antimicrobial peptides:molecular dynamics simulation studies

In this work, the role of the disulfide bridges in the maintenance of the secondary structure of the antimicrobial peptides androctonin, poly-phemusin-I, and thanatin is analyzed on the basis of their structural characteristics and of three of their respective mutants, andry4, poly4, and thany2, in which all the cysteine residues have been replaced with tyrosine residues. The absence of the disulfide bridges in andry4, poly4, and thany2 seems to be compensated by an overall enforcement of the original hydrogen bonds and by extra attractive interactions between the aromatic rings of the tyrosine residues. In spite of the mutations, the original β-hairpin structures are maintained in the three mutants, but the best conformational similarities are found for the androctonin/andry4 pair.

Antimicrobial Peptides from the Plants

AMPs （antimicrobial peptides） are small, mostly basic peptides that range in size from 2-9 kDa, and they are an important component of the innate defense system of plants where they are effector molecules considered to be an important defense barrier to pathogens and pests. Nine families of antimicrobial peptides have been identified in plants, including thionins, defensins, lipid transfer proteins, hevein and knotting-like peptides, four cysteine-types, and the recently reported shepherdins, snakins and cyclotides. They are part of both permanent and inducible defense barriers of plants. Transgenic overexpression of the corresponding genes leads to enhanced tolerance to pathogens, and peptide-sensitive pathogen mutants have reduced virulence. In this review, the recent studies on peptides from plant sources, including peptides isolated from indigenous medicine and edible plants of Central-Asia, are briefly discussed with a focus on their origins, antioxidant, antitumor activities and the possible mechanisms of actions in order to provide a profile of important plant peptides.

Junctional and somatic hypermutation-induced CX4C motif is critical for the recognition of a highly conserved epitope on HCV E2 by a human broadly neutralizing antibody

Induction of broadly neutralizing monoclonal antibodies(bNAbs)that bind to the viral envelope glycoproteins is a major goal of hepatitis C virus(HCV)vaccine research.The study of bNAbs arising in natural infection is essential in this endeavor.We generated a human antibody,8D6,recognizing the E2 protein of HCV isolated from a chronic hepatitis C patient.This antibody shows broadly neutralizing activity,which covers a pan-genotypic panel of cell culture-derived HCV virions(HCVcc).Functional and epitope analyses demonstrated that 8D6 can block the interaction between E2 and CD81 by targeting a highly conserved epitope on E2.We describe how the 8D6 lineage evolved via somatic hypermutation to achieve broad neutralization.We found that the V(D)J recombination-generated junctional and somatic hypermutation-induced disulfide bridge(C-C)motif in the CDRH3 is critical for the broad neutralization and binding activity of 8D6.This motif is conserved among a series of broadly neutralizing HCV antibodies,indicating a common binding model.Next,the 8D6 inferred germline(iGL)was reconstructed and tested for its binding affinity and neutralization activity.Interestingly,8D6 iGL-mediated relatively strong inhibition of the 1b genotype PR79L9 strain,suggesting that PR79L9 may serve as a potential natural viral strain that provides E2 sequences that induce bNAbs.Overall,our detailed epitope mapping and genetic studies of the HCV E2-specific mAb 8D6 have allowed for further refinement of antigenic sites on E2 and reveal a new mechanism to generate a functional CDRH3,while its iGL can serve as a probe to identify potential HCV vaccine strains.