Potent Macromolecule-Sized Poration of Lipid Bilayers by the Macrolittins, A Synthetically Evolved Family of Pore-Forming Peptides
| Autor: | Anna E. Pittman, Sarah Y. Kim, Gavin M. King, William C. Wimley, Sijia Li, Kalina Hristova |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Models Molecular Pore Forming Cytotoxic Proteins Lipid Bilayers Peptide 010402 general chemistry 01 natural sciences Biochemistry Catalysis Permeability 03 medical and health sciences Colloid and Surface Chemistry Peptide Library Amino Acid Sequence Peptide library Lipid bilayer Peptide sequence Phospholipids chemistry.chemical_classification Bilayer Vesicle Rational design General Chemistry Hydrogen-Ion Concentration 0104 chemical sciences 030104 developmental biology chemistry Biophysics Peptides Macromolecule |
| Zdroj: | Journal of the American Chemical Society. 140(20) |
| ISSN: | 1520-5126 |
| Popis: | Pore-forming peptides with novel functions have potential utility in many biotechnological applications. However, the sequence-structure-function relationships of pore forming peptides are not understood well enough to empower rational design. Therefore, in this work, we used synthetic molecular evolution to identify a novel family of peptides that are highly potent and cause macromolecular poration in synthetic lipid vesicles at low peptide concentration and at neutral pH. These unique 26-residue peptides, which we call macrolittins, release macromolecules from lipid bilayer vesicles made from zwitterionic PC lipids at peptide to lipid ratios as low as 1:1000, a property that is almost unprecedented among known membrane permeabilizing peptides. The macrolittins exist as membrane-spanning α-helices. They cause dramatic bilayer thinning and form large pores in planar supported bilayers. The high potency of these peptides is likely due to their ability to stabilize bilayer edges by a process that requires specific electrostatic interactions between peptides. |
| Databáze: | OpenAIRE |
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