Bombolitins are five natural heptadecapeptides originally isolated from the venom of a bumblebee. They induce lysis of erythrocytes and liposomes and increase the activity of phospholipase A2 (PLA2), that plays an important role in the early steps of the inflammatory process. It has been proposed that PLA2 activation depends on the alteration of the physical state of the membrane. Bombolitin II folds into an α-helix in a membrane mimicking environment constituted by sodium dodecyl sulfate micelles (Macromol. Chem. Phys., 196 (1995) 2827). In the present work, the topological orientation of the peptide relative to the micelle was determined, using three spin probes localized in different positions of the water/micelle system. The reduction in intensity of the 1H NMR signals clearly demonstrated that the peptide is located on the surface of the micelle, with its helical axis parallel to the interface. Only a small portion of the helix is exposed to the aqueous environment. Results from NMR experiments were confirmed by molecular dynamics simulations, performed using a two-phase water/decane simulation cell. The timescale for the reorientation of the peptide was between 120 and 450 ps, depending on the starting position of the peptide.

Interaction of Bombolitin II with a Membrane-mimetic Environment: an NMR and Molecular Dynamics Simulation Approach

MONTICELLI, LUCA;SCHIEVANO, ELISABETTA;MAMMI, STEFANO;PEGGION, EVARISTO
2002

Abstract

Bombolitins are five natural heptadecapeptides originally isolated from the venom of a bumblebee. They induce lysis of erythrocytes and liposomes and increase the activity of phospholipase A2 (PLA2), that plays an important role in the early steps of the inflammatory process. It has been proposed that PLA2 activation depends on the alteration of the physical state of the membrane. Bombolitin II folds into an α-helix in a membrane mimicking environment constituted by sodium dodecyl sulfate micelles (Macromol. Chem. Phys., 196 (1995) 2827). In the present work, the topological orientation of the peptide relative to the micelle was determined, using three spin probes localized in different positions of the water/micelle system. The reduction in intensity of the 1H NMR signals clearly demonstrated that the peptide is located on the surface of the micelle, with its helical axis parallel to the interface. Only a small portion of the helix is exposed to the aqueous environment. Results from NMR experiments were confirmed by molecular dynamics simulations, performed using a two-phase water/decane simulation cell. The timescale for the reorientation of the peptide was between 120 and 450 ps, depending on the starting position of the peptide.
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11577/2459413
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