Document Detail

Lipid composition is a determinant for human defensin HNP1 selectivity.
MedLine Citation:
PMID:  23193595     Owner:  NLM     Status:  In-Process    
Human neutrophilpeptide 1 (HNP1) is a human defensin with antimicrobial activity against different bacteria (both Gram-positive and negative), fungi, and viruses. HNP1 is stored in the cytoplasmic azurophilic granules of neutrophils. To elucidate the mode of action of this antimicrobial peptide, studies based on its lipid selectivity were carried out. Large unilamellar vesicles with different lipid compositions were used as biomembranes model systems (mammal, fungal, and bacterial models). Changes on the intrinsic fluorescence of HNP1 upon membrane binding/insertion show that HNP1 has quite distinct preferences for mammalian and fungal membrane model systems. HNP1 showed low interaction with glucosylceramide rich membranes, but high sterol selectivity: it has a higher partition for ergosterol-containing membranes (as fungal membranes) and lower interaction with cholesterol-containing membranes (as in mammalian cells). These results reveal that lipid selectivity is a determinant step for HNP1 action. Fluorescence quenching data obtained using acrylamide indicate that HNP1 interacts with membranes without a full insertion in the lipid bilayer. Generalized polarization of laurdan indicates a change in membrane fluidity in the presence of HNP1 for POPC membranes but not for ergosterol-enriched membranes.
Sónia Gonçalves; João Abade; Alexandre Teixeira; Nuno C Santos
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Biopolymers     Volume:  98     ISSN:  0006-3525     ISO Abbreviation:  Biopolymers     Publication Date:  2012  
Date Detail:
Created Date:  2012-11-29     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0372525     Medline TA:  Biopolymers     Country:  United States    
Other Details:
Languages:  eng     Pagination:  313-21     Citation Subset:  IM    
Instituto de Medicina Molecular, Faculdade de Medicina da Universidade de Lisboa, Lisbon, Portugal.
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