Hemin and bile pigments are the secondary structure regulators of intrinsically disordered antimicrobial peptides

Ferenc Zsila, Tünde Juhász, Szilvia Bősze, Kata Horváti, Tamás Beke-Somfai

Research output: Contribution to journalArticle

8 Citations (Scopus)


The interaction of protoporphyrin compounds of human origin with the major bee venom component melittin (26 a.a., Z +6) and its hybrid derivative (CM15, 15 a.a., Z +6) were studied by a combination of various spectroscopic methods. Throughout a two-state, concentration-dependent process, hemin and its metabolites (biliverdin, bilirubin, bilirubin ditaurate) increase the parallel β-sheet content of the natively unfolded melittin, suggesting the oligomerization of the peptide chains. In contrast, α-helix promoting effect was observed with the also disordered but more cationic CM15. According to fluorescence quenching experiments, the sole Trp residue of melittin is the key player during the binding, in the vicinity of which the first pigment molecule is accommodated presumably making indole-porphyrin π-π stacking interaction. As circular dichroism titration data suggest, cooperative association of additional ligands subsequently occurs, resulting in multimeric complexes with an apparent dissociation constant ranged from 20 to 65 μM. Spectroscopic measurements conducted with the bilirubin catabolite urobilin and stercobilin refer to the requirement of intact dipyrrinone moieties for inducing secondary structure transformations. The binding topography of porphyrin rings on a model parallel β-sheet motif was evaluated by absorption spectroscopy and computational modeling showing a slipped-cofacial binding mode responsible for the red shift and hypochromism of the Soret band. Our results may aid to recognize porphyrin-responsive binding motifs of biologically relevant, intrinsically disordered peptides and proteins, where transient conformations play a vital role in their functions.

Original languageEnglish
Pages (from-to)195-205
Number of pages11
Issue number2
Publication statusPublished - Feb 2018


  • CM15
  • bilirubin
  • biliverdin
  • circular dichroism spectroscopy
  • fluorescence quenching
  • hemin
  • intrinsic disorder
  • melittin

ASJC Scopus subject areas

  • Analytical Chemistry
  • Catalysis
  • Pharmacology
  • Drug Discovery
  • Spectroscopy
  • Organic Chemistry

Fingerprint Dive into the research topics of 'Hemin and bile pigments are the secondary structure regulators of intrinsically disordered antimicrobial peptides'. Together they form a unique fingerprint.

  • Cite this