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Insights into the Antimicrobial Mechanism of Action of Human RNase6: Structural
Determinants for Bacterial Cell Agglutination and Membrane Permeation
#MMPMID27089320
Pulido D
; Arranz-Trullén J
; Prats-Ejarque G
; Velázquez D
; Torrent M
; Moussaoui M
; Boix E
Int J Mol Sci
2016[Apr]; 17
(4
): 552
PMID27089320
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Human Ribonuclease 6 is a secreted protein belonging to the ribonuclease A
(RNaseA) superfamily, a vertebrate specific family suggested to arise with an
ancestral host defense role. Tissue distribution analysis revealed its expression
in innate cell types, showing abundance in monocytes and neutrophils. Recent
evidence of induction of the protein expression by bacterial infection suggested
an antipathogen function in vivo. In our laboratory, the antimicrobial properties
of the protein have been evaluated against Gram-negative and Gram-positive
species and its mechanism of action was characterized using a membrane model.
Interestingly, our results indicate that RNase6, as previously reported for
RNase3, is able to specifically agglutinate Gram-negative bacteria as a main
trait of its antimicrobial activity. Moreover, a side by side comparative
analysis with the RN6(1-45) derived peptide highlights that the antimicrobial
activity is mostly retained at the protein N-terminus. Further work by site
directed mutagenesis and structural analysis has identified two residues involved
in the protein antimicrobial action (Trp1 and Ile13) that are essential for the
cell agglutination properties. This is the first structure-functional
characterization of RNase6 antimicrobial properties, supporting its contribution
to the infection focus clearance.
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