The interactions of neuropeptides with membrane model systems: A case study

Abstract

The interactions between the positively charged neuropeptides substance P (SP), bradykinin (BK), and zwitterionic Met-enkephalin (ME) neuropeptides, and negatively charged SDS and zwitterionic lysophosphatidylcholine (LPC) membrane model systems, have been investigated using one- and two-dimensional nmr experiments. Proton longitudinal relaxation studies were used to characterize these interactions as intrinsic or extrinsic. An extrinsic interaction are similar to those observed for extrinsic membrane proteins. An intrinsic interaction are similar to those observed for intrinsic membrane proteins, and would require that the hydrophobic residues penetrate or insert into the hydrophobic core of the membrane. The interactions between both SP and BK and SDS, based on nmr results, may be characterized as intrinsic, and the interaction between ME and SDS may be characterized as extrinsic. Two-dimensional nuclear Overhauser enhancement spectroscopy experiments proved the insertion of the phenylalanine residues on both SP and BK into the hydrophobic core of SDS micelles. The interaction between SP and BK with LPC based on nmr results are characterized as extrinsic, with the interaction between ME and SDS characterized as weakly intrinsic.

Comparison of the conformation and electrostatic surface properties of magainin peptides bound to sodium dodecyl sulfate and dodecylphosphocholine micelles

“…Two-dimensional NMR and molecular modeling investigations indicated that (Ala 8,13,18 )magainin 2 amide bound to DPC micelles adopts a ␣-helical secondary structure involving residues 2-16. The four C-terminal residues converge to a lose ␤-turn structure.…”

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Abstract: The role played by noncovalent interactions in inducing a stable secondary structure onto the sodium dodecyl sulfate (SDS) and dodecylphosphocholine (DPC) micelle-bound conformations of (Ala 8,13,18 )magainin 2 amide and the DPC micelle bound conformation of magainin 1 were determined. Two-dimensional NMR and molecular modeling investigations indicated that (Ala 8,13,18 )magainin 2 amide bound to DPC micelles adopts a ␣-helical secondary structure involving residues 2-16.

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Calcium‐binding properties and molecular organization of bradykinin

“…Such a high degree of flexibility suggests that binding to the receptor implies the selection of a particular structure from among the number of slowly or rapidly interconverting ones in solution. As a matter of fact, enhancement of the b-turn-forming potential of bradykinin was observed in the presence of SDS micelles [16,24±27], apolar organic solvents [14,18,20,27] or aqueous phospholipids [13,22,26]; as a consequence of all these findings, bradykinin is currently believed to adopt a C-terminal b turn upon complexation with the receptor [28].In the present study, NMR data were collected for bradykinin in dimethylsulfoxide containing 1% water in the presence of calcium, in order to ascertain whether the conformational equilibria and structural heterogeneity are affected by a divalent metal ion that may act as a mediator in the process of conformational selection. The water/dimethylsulfoxide solvent was chosen because most biochemical functions occur away from bulk water but may involve active molecules that retain some water of hydration.…”

Structural and Functional Characterization of CRAMP-18 Derived from a Cathelicidin-Related Antimicrobial Peptide CRAMP

“…Temperature coefficients were calculated from the TOCSY experiments at three different temperatures (288, 298, and 308 K) to investigate the intramolecular hydrogen bondings in the peptides. 19 NMR spectroscopy can give useful information about the interaction between the peptides and micelles. NOESY experiments for the sample in non-deuterated SDS micelles was executed at 298 K with mixing times of 250 and 600 ms. All NMR spectra were processed off-line using the FELIX software package on SGI (Molecular Simulations Inc., San Diego, CA, USA).…”