1xkm
From Proteopedia
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| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
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NMR structure of antimicrobial peptide distinctin in water
Overview
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 stabilizes distinctin against proteases compared with other linear amphipathic peptides, without affecting its antimicrobial, hemolytic, and ion-channel formation properties after membrane interaction. This full-parallel helical orientation represents a perfect compromise between formation of a stable structure in water and requirement of a drastic structural rearrangement in membranes to elicit antimicrobial potential. Thus, distinctin can be claimed as a prototype of a previously unrecognized class of antimicrobial derivatives. These results suggest a critical revision of the role of peptide oligomerization whenever solubility or resistance to proteases is known to affect biological properties.
About this Structure
1XKM is a Protein complex structure of sequences from [1]. Full crystallographic information is available from OCA.
Reference
A folding-dependent mechanism of antimicrobial peptide resistance to degradation unveiled by solution structure of distinctin., Raimondo D, Andreotti G, Saint N, Amodeo P, Renzone G, Sanseverino M, Zocchi I, Molle G, Motta A, Scaloni A, Proc Natl Acad Sci U S A. 2005 May 3;102(18):6309-14. Epub 2005 Apr 19. PMID:15840728
Page seeded by OCA on Mon Mar 31 00:50:55 2008
