Structure of Transmembrane Pores Stabilized by Antimicrobial Peptides Magainin and PGLa

Abstract

Antimicrobial peptides are found in many organisms as part of their defense system against bacterial infections. They have similar structural and functional features: most consist of amphiphilic helices that bind to a membrane and disrupt it by diverse methods. Among these peptides, magainin 2 and PGLa are found in the frog skin and exhibit synergistic effects in lipid bilayer disruption by the formation of transmembrane pores [1]. Experimental methods, such as solid-state NMR, have shed light on the relative orientation of magainin 2 and PGLa on membranes with different lipid composition [2,3], but there is a general lack of information on the structure of the pore and the specific interactions that lead to its stabilization. In the present work, we studied the structure and dynamics of transmembrane pores formed by magainin 2 and magainin 2/PGLa (2:2) tetramers by all-atom molecular dynamics simulations performed at the Anton supercomputer (Pittsburgh Supercomputing Center). For both systems we observed stabilization of a pore. The 9-μs simulation time allows a detailed analysis of its structure and properties, the role of the lipids surrounding it, and the relative orientation of magainin 2 and PGLa in the membrane.