Selforganized peptide lipid complexes:

1
Self-organized peptide lipid complexes Peptide
induced transmembrane water pores.
2
Dynamic, not static !! Transformations driven
by lipid physics
Complex lipid-protein interplay Many
different species
3
Pore formation in lipid bilayers.
Continuous lipid matrix
Partial breakdown required for
Transport of ions and small molecules
Membrane fusion

4
Pore formation in lipid bilayers.
Pores formed during the spontaneous
aggregation of the DPPC bilayer. -Application of
lateral tension -The membrane curves at the
openings of the pore. The lipids locally
perturbed. -Hour-glass shape or toroidal pore.
water pore
5
Metastable Pores Pore Closure
S.J. Marrink
6
Models for peptide induced pore formation.
barrel stave carpet
toroidal pore
mode of action of magainin ?
7
Pore formation by antimicrobial peptides
Magainins

• Short cationic peptides from the skin of Xenopus
  Leavis (African clawed frog).
• Permeabilize the lipid matrix -gt cell death.
• Bind preferentially to anionic lipids i.e. outer
  membrane of the bacterial cells.
• Broad antibacterial and anticancer activity (not
  hemolytic).
• Suggest formation of a toroidal pore (Neutron
  scattering).

toroidal

• What is known
• bind to membrane.
• aggregate.
• form pore (release ions).

Proposed General mechanism
8
Magainin H2 (MG-H2)
sequence
q
q
q
SER
ILE
ILE
LYS
LYS
PHE
LEU
HIS
ILE
TPR
LYS
PHE
GLY
LYS
ALA
PHE
VAL
GLY
GLU
ILE
MET
q
-q
ASN
ILE
23 amino acids total charge 3
properties -amphipatic -binds to zwitterionic
lipids -structure 50 a-helical (CD spectra in
the presence of PCs) -forms pores by cooperative
action -pore diameter 2nm -proposed to form a
toroidal pore
9
Magainin H2 (MG-H2)
1 copy initially placed randomly in solution (no
tension)

• Migrates to interface
• Embeds
• Partial helical structure
• no pore

Hari Leontiadou
10
Magainin H2 (MG-H2)
2 copies placed in solution P/L 132 (tension
20mN/m)

• Migrates to interface
• Embeds
• Significant helical structure
• PORE FORMATION

Hari Leontiadou
11
One peptide, nothing happens Two peptides,
still nothing happens. Four peptides, however
LYS
PHE/TRP
12
4 copies initially in the solution P/L 116 no
tension
Magainin H2 (MG-H2)

• Aggregates
• Migrates to interface
• Embeds
• Spontaneous
• PORE FORMATION

Hari Leontiadou
13
(No Transcript)
14
Magainin H2 (MG-H2)

• Asymmetric binding of peptides induces stress in
  second layer.
• Spontaneous formation of pore.
• Pore stabilized by binding primarily to the
  entrance of the pore.
• Collapse of pore as peptides migrate through the
  pore?

?

• Advantages
• Simple
• Does not require insertion of peptides into
  lipid matrix.
• Pore metastable.