TY - JOUR
T1 - The amphibian antimicrobial peptide uperin 3.5 is a cross-alpha/cross-beta chameleon functional amyloid
AU - Salinas, Nir
AU - Tayeb-Fligelman, Einav
AU - Sammito, Massimo D.
AU - Bloch, Daniel
AU - Jelinek, Raz
AU - Noy, Dror
AU - Usón, Isabel
AU - Landau, Meytal
N1 - Publisher Copyright: © 2021 National Academy of Sciences. All rights reserved.
PY - 2021/1/11
Y1 - 2021/1/11
N2 - Antimicrobial activity is being increasingly linked to amyloid fibril formation, suggesting physiological roles for some human amyloids, which have historically been viewed as strictly pathological agents. This work reports on formation of functional cross-α amyloid fibrils of the amphibian antimicrobial peptide uperin 3.5 at atomic resolution, an architecture initially discovered in the bacterial PSMα3 cytotoxin. The fibrils of uperin 3.5 and PSMα3 comprised antiparallel and parallel helical sheets, respectively, recapitulating properties of β-sheets. Uperin 3.5 demonstrated chameleon properties of a secondary structure switch, forming mostly cross-β fibrils in the absence of lipids. Uperin 3.5 helical fibril formation was largely induced by, and formed on, bacterial cells or membrane mimetics, and led to membrane damage and cell death. These findings suggest a regulation mechanism, which includes storage of inactive peptides as well as environmentally induced activation of uperin 3.5, via chameleon cross-α/β amyloid fibrils.
AB - Antimicrobial activity is being increasingly linked to amyloid fibril formation, suggesting physiological roles for some human amyloids, which have historically been viewed as strictly pathological agents. This work reports on formation of functional cross-α amyloid fibrils of the amphibian antimicrobial peptide uperin 3.5 at atomic resolution, an architecture initially discovered in the bacterial PSMα3 cytotoxin. The fibrils of uperin 3.5 and PSMα3 comprised antiparallel and parallel helical sheets, respectively, recapitulating properties of β-sheets. Uperin 3.5 demonstrated chameleon properties of a secondary structure switch, forming mostly cross-β fibrils in the absence of lipids. Uperin 3.5 helical fibril formation was largely induced by, and formed on, bacterial cells or membrane mimetics, and led to membrane damage and cell death. These findings suggest a regulation mechanism, which includes storage of inactive peptides as well as environmentally induced activation of uperin 3.5, via chameleon cross-α/β amyloid fibrils.
KW - amyloid
KW - antimicrobial peptides
KW - cross-alpha
KW - functional fibril
UR - http://www.scopus.com/inward/record.url?scp=85099149569&partnerID=8YFLogxK
U2 - https://doi.org/10.1073/pnas.2014442118
DO - https://doi.org/10.1073/pnas.2014442118
M3 - مقالة
C2 - 33431675
SN - 0027-8424
VL - 118
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 3
M1 - e2014442118
ER -