Helix Fraying and Lipid-Dependent Structure of a Short Amphipathic Membrane-Bound Peptide Revealed by Solid-State NMR
| Autor: | Erik Strandberg, Anne S. Ulrich, Francesc Rabanal, Jochen Bürck, Parvesh Wadhwani, Ariadna Grau-Campistany |
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| Rok vydání: | 2018 |
| Předmět: |
Protein Conformation
alpha-Helical 0301 basic medicine Circular dichroism Membrane bound Lipid Bilayers Peptide Membranes (Biology) 010402 general chemistry 01 natural sciences 03 medical and health sciences Membranes (Biologia) Amphiphile Materials Chemistry Amino Acid Sequence Physical and Theoretical Chemistry Nuclear Magnetic Resonance Biomolecular chemistry.chemical_classification Chemistry Circular Dichroism Nuclear magnetic resonance spectroscopy 0104 chemical sciences Surfaces Coatings and Films Crystallography 030104 developmental biology Membrane Solid-state nuclear magnetic resonance Phosphatidylcholines lipids (amino acids peptides and proteins) Pèptids Peptides Alpha helix |
| Zdroj: | Dipòsit Digital de la UB Universidad de Barcelona |
| ISSN: | 1520-5207 1520-6106 |
| DOI: | 10.1021/acs.jpcb.8b02661 |
| Popis: | The amphipathic a-helical peptide KIA14 [(KIAGKIA)(2)-NH2] was studied in membranes using circular dichroism and solid-state NMR spectroscopy to obtain global as well as local structural information. By analyzing H-2 NMR data from 10 analogues of KIA14 that were selectively labeled with Ala-d(3), those positions that are properly folded into a helix could be determined within the membrane-bound peptide. The N-terminus was found to be unraveled, whereas positions 4-14 formed an ideal helix all the way to the C-terminus. The helicity did not change when Gly residues were replaced by Ala-d3 but was reduced when Ile was replaced, indicating that large hydrophobic residues are required for membrane binding and helix formation. The reduced helicity was strongly correlated with a decrease in peptide-induced leakage from lipid vesicles. The orientation of the short KIA14 peptide was assessed in several lipid systems and compared with that of the longer KIA21 sequence [(KIAGKIA)(3)-NH2]. In 1,2-dioleoylsn-glycero-3-phosphatidylcholine, both peptides are aligned flat on the membrane surface, whereas in 1,2-dimyristoyl-sn-glycero3-phosphatidylcholine (DMPC)/1-myristoy1-2-hydroxy-sn-glycero-3-phosphatidylcholine (lyso-MPC) both are inserted into the membrane in an upright orientation. These two types of lipid systems had been selected for their strongly negative and positive spontaneous curvature, respectively. We propose that in these cases, the peptide orientation is largely determined by the lipid properties. On the other hand, in plain DMPC and 1,2-dilauroyl-sn-glycero-3-phosphatidylcholine, which have only a slight positive curvature, a marked difference in orientation is evident: the short KIA14 lies almost flat on the membrane surface, whereas the longer KIA21 is more tilted. We thus propose that out of the lipid systems tested here, DMPC (with hardly any curvature) is the least biased,lipid system in which peptide orientation and realignment can be studied, allowing to compare and discriminate the intrinsic effects of the properties of the peptides as such. |
| Databáze: | OpenAIRE |
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