How a short pore forming peptide spans the lipid membrane

TY - JOUR

T1 - How a short pore forming peptide spans the lipid membrane

AU - Vestergaard, Mikkel

AU - Christensen, Mikkel

AU - Hansen, Sara K.

AU - Gronvall, Dennis

AU - Kjolbye, Lisbeth R.

AU - Vosegaard, Thomas

AU - Schiott, Birgit

PY - 2017/6/1

Y1 - 2017/6/1

N2 - Many antimicrobial peptides function by forming pores in the plasma membrane of the target cells. Intriguingly, some of these peptides are very short, and thus, it is not known how they can span the membrane, or whether other mechanisms of cell disruption are dominant. Here, the conformation and orientation of the 14-residue peptaibol SPF-5506-A4 (SPF) are investigated in lipid environments by atomistic and coarse grained molecular dynamics (MD) simulations, circular dichroism, and nuclear magnetic resonance (NMR) experiments. The MD simulations show that SPF is inserted spontaneously in a transmembrane orientation in both 1, 2-dimyristoyl-snglycero-3-phosphocholine and 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine bilayers resulting in thinning of the bilayers near the peptides, which drives the peptide aggregation. Furthermore, the backbone conformation of the peptide in the bilayer bound state is different from that of the NMR model solved in small bicelles. These results demonstrate that mutual adaption between the peptides and the membrane is likely to be important for pore formation.

AB - Many antimicrobial peptides function by forming pores in the plasma membrane of the target cells. Intriguingly, some of these peptides are very short, and thus, it is not known how they can span the membrane, or whether other mechanisms of cell disruption are dominant. Here, the conformation and orientation of the 14-residue peptaibol SPF-5506-A4 (SPF) are investigated in lipid environments by atomistic and coarse grained molecular dynamics (MD) simulations, circular dichroism, and nuclear magnetic resonance (NMR) experiments. The MD simulations show that SPF is inserted spontaneously in a transmembrane orientation in both 1, 2-dimyristoyl-snglycero-3-phosphocholine and 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine bilayers resulting in thinning of the bilayers near the peptides, which drives the peptide aggregation. Furthermore, the backbone conformation of the peptide in the bilayer bound state is different from that of the NMR model solved in small bicelles. These results demonstrate that mutual adaption between the peptides and the membrane is likely to be important for pore formation.

KW - MOLECULAR-DYNAMICS

KW - FORCE-FIELD

KW - 14-RESIDUE PEPTAIBOLS

KW - ANTIMICROBIAL PEPTIDE

KW - HARZIANINS HC

KW - SIMULATIONS

KW - PROTEINS

KW - TRICHODERMA

KW - BILAYERS

KW - SPF-5506-A(4)

UR - http://www.scopus.com/inward/record.url?scp=85019036673&partnerID=8YFLogxK

U2 - 10.1116/1.4982642

DO - 10.1116/1.4982642

M3 - Journal article

C2 - 28476091

SN - 1934-8630

VL - 12

JO - Biointerphases

JF - Biointerphases

IS - 2

M1 - 02D405

ER -