A folding-dependent mechanism of antimicrobial peptide resistance to degradation unveiled by solution structure of distinctin.

ABSTRACT: Many bioactive peptides, presenting an unstructured conformation in aqueous solution, are made resistant to degradation by posttranslational modifications. Here, we describe how molecular oligomerization in aqueous solution can generate a still unknown transport form for amphipathic peptides, which is more compact and resistant to proteases than forms related to any possible monomer. This phenomenon emerged from 3D structure, function, and degradation properties of distinctin, a heterodimeric antimicrobial compound consisting of two peptide chains linked by a disulfide bond. After homodimerization in water, this peptide exhibited a fold consisting of a symmetrical full-parallel four-helix bundle, with a well secluded hydrophobic core and exposed basic residues. This fold significantly stab

SUBMITTER: Raimondo D 

PROVIDER: S-EPMC1088359 | biostudies-literature | 2005 May

REPOSITORIES: biostudies-literature