Abstract of the PDB Structure's related Publication:
Intragenic antimicrobial peptides (IAPs) are internal sequences of proteins with physicochemical similarities to Antimicrobial Peptides (AMPs) that, once identified and synthesized as individual entities, present antimicrobial activity. Many mature proteins encoded by the genomes of virtually any organism may be regarded as inner reservoirs of IAPs, conferring them ample biotechnological potential. However, IAPs may also share shortcomings with AMPs, such as low half-life in biological media and non-specific adsorption in eukaryotic cells. The present manuscript reports a translational approach that encompasses the uncovering of two novel IAPs from human proteins as well as the first results concerning the incorporation and sustained release of one of these peptides from ureasil-polyether hybrid polymeric films. For such, the software Kamal was used to scan putative IAPs in the human proteome, and two peptides, named Hs05 and Hs06, were identified, synthesized, and tested as antimicrobials. Biophysical assays were conducted using model phospholipid vesicles and 1H NMR solution structures in phospholipid micelles were obtained for the IAP Hs05. This peptide was incorporated in a polymeric matrix composed of the ureasil/PPO-PEO-PPO triblock copolymer, and the resulting films were evaluated by atomic force microscopy and imaging mass spectrometry. The release rate of Hs05 from the polymeric matrix was assessed and the antimicrobial activity of Hs05-loaded hybrid polymeric films was evaluated against the bacterium Escherichia coli. This study represents the first steps towards the development of polymeric films enriched with IAPs obtained from the human proteome as sustained release devices for topical application.
NAT10 is the human homolog of yeast RRA1. It is a disease-associated gene (progeria, laminopathies). NAT10 is required for the formation of two ac4C in human SSU rRNA: one in helix 34, predicted, based on the yeast work, to map to position 1338, and one in helix 45, predicted to be at position 1843. siRNA-mediated depletion of NAT10 also leads to loss of tRNA acetylation. NAT10 interacts in vivo in human cells with THUMPD1, the homolog of TAN1, and a NAT10/THUMPD1 complex is suggested to work in tRNA acetylation in human, similar to the KRE33/TAN1 complex in budding yeast. NAT10 complements both 18S rRNA and tRNA acetylation in yeast.