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Mammalian antimicrobial peptide protegrin‐4 self assembles and forms amyloid‐like aggregates: Assessment of its functional relevance
Author(s) -
Gour Shalini,
Kumar Vijay,
Singh Ashutosh,
Gadhave Kundlik,
Goyal Pankaj,
Pandey Janmejay,
Giri Rajanish,
Yadav Jay Kant
Publication year - 2019
Publication title -
journal of peptide science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.475
H-Index - 66
eISSN - 1099-1387
pISSN - 1075-2617
DOI - 10.1002/psc.3151
Subject(s) - peptide , thioflavin , antimicrobial peptides , antimicrobial , congo red , chemistry , amyloid (mycology) , innate immune system , bacillus subtilis , biochemistry , in vitro , amino acid , cysteine , antibacterial peptide , biology , biophysics , bacteria , microbiology and biotechnology , antibacterial activity , enzyme , medicine , inorganic chemistry , genetics , receptor , disease , organic chemistry , pathology , adsorption , alzheimer's disease
Protegrin‐4 (PG‐4) is a member of the porcine leukocyte protegrins family of cysteine‐rich antimicrobial peptides (AMPs) isolated from Sus scrofa . It consists of 18 amino acid residues and works as a part of innate immune system. In this study, we examined the intrinsic aggregation propensity of this AMP using multiple computational algorithms, namely, TANGO, AGGRESCAN, FOLDAMYLOID, AMYLPRED, and ZYGGREGATOR, and found that the peptide is predicted to have a high propensity for the β sheet formation that disposes this peptide to be amyloidogenic. Under in vitro conditions, PG‐4 formed visible aggregates and displayed the hallmark properties of typical amyloids such as enhanced binding of Congo red, increased fluorescence with Thioflavin‐T, and fibrillar morphology under transmission electron microscopy. Then we examined its antimicrobial activity against Bacillus subtilis and found that the aggregated peptide retained its antimicrobial activity. Additionally, the aggregates remain non‐toxic to the HEK293 and Caco2 cells. Our study suggests that the inherent aggregation properties of AMP can rationally be explored as a potential source of peptide‐based antimicrobials with enhanced stability.