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SHR Neuro Cancer Cardio Lipid Metab Microb
Hodzic, A; Vejzovic, D; Topciu, A; Kuhlmann, K; Kumar, R; Mroginski, MA; de, Miguel, A; Hofmann, P; Zangger, K; Weingarth, M; Cordfunke, RA; Drijfhout, JW; Nibbering, P; Belicka, M; Lohner, K; Malanovic, N.
SAAP-148 Oligomerizes into a Hexamer Forming a Hydrophobic Inner Core.
Chembiochem. 2025; 26(12):e202500112
Doi: 10.1002/cbic.202500112
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- Vejzovic Djenana
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- Abstract:
- Human cathelicidin LL-37 derivative, the 24-mer SAAP-148, is highly effective in vitro in eradicating multidrug-resistant bacteria without inducing resistance. SAAP-148 has a high cationic charge (+11) and 46% hydrophobicity, which, once the peptide folds into an alpha helix, forms a wide hydrophobic face. This highly amphipathic nature facilitates on the one hand its insertion into the membrane's fatty acyl chain region and on the other hand it´s interaction with anionic membrane components, which aids in killing bacteria. However, the contributions of the secondary and quaternary structures have not been thoroughly investigated so far. To address this, we applied circular dichroism, NMR spectroscopy, X-ray scattering, AlphaFold 3 protein folding software, and molecular dynamics simulations. Our results reveal that SAAP-148 adopts a stable hexameric bundle composed of three parallel dimers, that together form a hydrophobic core of aromatic side chain residues. The hexameric structure is retained at the membrane interface, whereby, MD simulation studies indicated the formation of a fiber-like structure in the presence of anionic membranes. This certainly seems plausible, as oligomers are stabilized by aromatic residues, and the exposure of positively charged side chains on the surface likely facilitates the transition of the peptide into fibrils on anionic membranes.
- Find related publications in this database (using NLM MeSH Indexing)
- Hydrophobic and Hydrophilic Interactions - administration & dosage
- Molecular Dynamics Simulation - administration & dosage
- Antimicrobial Cationic Peptides - chemistry
- Humans - administration & dosage
- Protein Multimerization - administration & dosage
- Cathelicidins - chemistry