We studied amidated and non-amidated piscidins 1 and 3, amphipathic cationic antimicrobial peptides from fish, to characterize functional and structural similarities and differences between these peptides and better understand the structural motifs involved in biological activity and functional diversity among amidated and non-amidated isoforms. Antimicrobial and hemolytic assays were carried out to assess their potency and toxicity, respectively. Site-specific high-resolution solid-state NMR orientational restraints were obtained from (15)N-labeled amidated and non-amidated piscidins 1 and 3 in the presence of hydrated oriented lipid bilayers. Solid-state NMR and circular dichroism results indicate that the peptides are alpha-helical and oriented parallel to the membrane surface. This orientation was expected since peptide-lipid interactions are enhanced at the water-bilayer interface for amphipathic cationic antimicrobial peptides. (15)N solid-state NMR performed on oriented samples demonstrate that piscidin experiences fast, large amplitude backbone motions around an axis parallel to the bilayer normal. Under the conditions tested here, piscidin 1 was confirmed to be more antimicrobially potent than piscidin 3 and antimicrobial activity was not affected by amidation. In light of functional and structural similarities between piscidins 1 and 3, we propose that their topology and fast dynamics are related to their mechanism of action.
Subtelomeres are concentrations of interchromosomal segmental duplications capped by telomeric repeats at the ends of chromosomes. The nature of the segments shared by different sets of human subtelomeres reflects their high rate of recent interchromosomal exchange. Here, we characterize the rearrangements incurred by the 15q subtelomere after it arose from a chromosome fission event in the common ancestor of great apes. We used FISH, sequencing of genomic clones, and PCR to map the breakpoint of this fission and track the fate of flanking sequence in human, chimpanzee, gorilla, orangutan, and macaque genomes. The ancestral locus, a cluster of olfactory receptor (OR) genes, lies internally on macaque chromosome 7. Sequence originating from this fission site is split between the terminus of 15q and the pericentromere of 14q in the great apes. Numerous structural rearrangements, including interstitial deletions and transfers of material to or from other subtelomeres, occurred subsequent to the fission, such that each species has a unique 15q structure and unique collection of ORs derived from the fission locus. The most striking rearrangement involved transfer of at least 200 kb from the fission-site region to the end of chromosome 4q, where much still resides in chimpanzee and gorilla, but not in human. This gross structural difference places the subtelomeric defect underlying facioscapulohumeral muscular dystrophy (FSHD) much closer to the telomere in human 4q than in the hybrid 4q-15q subtelomere of chimpanzee.[Supplemental material is available online at www.genome.org. The sequence data from this study have been submitted to GenBank under accession nos. AC188481, AC183330, AC150715, AC149242, AC148620, AC148535, AC173434, AC186245, AC205763, AC150448, AC183669, AC197422.]Subtelomeres are composed of interchromosomally duplicated sequences situated near the ends of chromosomes just proximal of telomeric repeats (Mefford and Trask 2002). Roughly half of the subtelomeric sequence in the human genome has moved or changed copy number since human and chimpanzee diverged (Linardopoulou et al. 2005). Due to this recent change, most subtelomeric duplications show variation in chromosomal location and copy number in the human population. Assays of the content of subtelomeres in other primates by fluorescence in situ hybridization (FISH) have revealed significant differences among species (Kingsley et al. 1997;Trask et al. 1998;Martin et al. 2002;van Geel et al. 2002b;Linardopoulou et al. 2005). However, no study has yet traced the evolution of a given subtelomere in primates by comparative analyses at the sequence level.The evolution of subtelomeres is "reticulate" (Jackson et al. 2005;Huson and Bryant 2006). Recurrent shuffling of material among ends makes it difficult to distinguish structures that are identical by descent from the shared presence (or absence) of particular sequences. Gene conversion-like transfers between duplicated segments can obfuscate the timing of the original duplication. In order to reconstru...
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.