Structural analysis and mode of action of BMAP-27, a cathelicidin-derived antimicrobial peptide.

Abstract:

:BMAP-27, a member of cathelicidin family, plays an important role against microorganisms, including bacteria and fungi. BMAP-27 may exert antimicrobial effects through membrane integrity disruption, but the exact molecular mechanism remains unclear. To identify the structural features important for antimicrobial activity and propose a mechanism underlying antibacterial effects, we determined the nuclear magnetic resonance structure of BMAP-27 in a membrane-mimetic environment and investigated its interactions with lipid membranes. BMAP-27 exhibited a long N-terminal α-helix with faces patterned into aromatic and cationic regions, central kink, and short hydrophobic C-terminal helix. While the N-terminal 18-residue peptide (BMAP-18) exerted only antibacterial activity, BMAP-27 showed potent activity against bacteria and cancer cells. Both peptides inhibited bacterial growth, but BMAP-18 showed delayed bactericidal activity and BMAP-27 completely killed bacteria within 20 min. The differences in antimicrobial activities and microbicidal kinetics may be associated with membrane permeabilisation; BMAP-27 rapidly and largely disrupted membrane integrity, whereas BMAP-18 showed low membrane disruption activity. Thus, the N-terminal helix is sufficient to inhibit bacterial growth and the C-terminal helix is involved in membrane permeabilisation for rapid bactericidal and efficient anticancer activities. The structural and functional characterisation of BMAP-27 may encourage the development of novel antimicrobial/anticancer agents.

journal_name

Peptides

journal_title

Peptides

authors

Yang S,Lee CW,Kim HJ,Jung HH,Kim JI,Shin SY,Shin SH

doi

10.1016/j.peptides.2019.170106

subject

Has Abstract

pub_date

2019-08-01 00:00:00

pages

170106

eissn

0196-9781

issn

1873-5169

pii

S0196-9781(19)30084-1

journal_volume

118

pub_type

杂志文章

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