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Streltsov VA, Varghese JN, Masters CL, Nuttall SD. Crystal structure of the amyloid-β p3 fragment provides a model for oligomer formation in Alzheimer's disease. J Neurosci. 2011 Jan 26;31(4):1419-26. PubMed.
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Massachusetts General Hospital & Harvard Medical School
The study describes an elegant tool for what has been a frustrating problem. Of particular interest to us, this study shows that Aβ dimers have striking structural similarities to the dimeric forms of the antimicrobial peptides human NP2, horseshoe crab tachystatin B, and mouse α-defensin. We recently reported on the antimicrobial activity of Aβ, and our newest data suggest dimerization is a key event in turning relatively inactive Aβ monomers into forms that can attack bacteria.
This is not a phenomenon restricted to Aβ. It has been known for some time that oligomerization has an important role in the action and targeting of a number of antimicrobial proteins (AMPs), including the archetypal antimicrobial peptide LL-37 which can form oligomers, fibrils, and birefringent amyloid (albeit, LL-37 amyloid has only been observed in vitro to date). Oligomerization is also a key mechanism for antimicrobial protein-mediated agglutination and inactivation of viral particles.
Despite this central role in AMP mechanisms, relatively few studies have characterized the oligomerization of antimicrobial peptides. Potentially, studies like this one could help us understand the cytotoxic action of not only Aβ, but AMPs as well. Notably, using conditions developed to promote Aβ oligomerization, we have generated LL-37 dimers with potentiated activity that are also resistant to bacterial defense proteases targeted at AMPs.
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