1. Peptide-membrane Interactions: Peptide Insertion
and Induced Hole Formation
Yonghua Deng & Guanghong Wei
Department of Physics, Fudan University, Shanghai , China
Figure 2: Top view: water not showed
protein in red,
Lipid in cyan
Figure 1: Side view: lipid not showed, P atoms in cyan, water in yellow
≈0.7 nm
Initial:0 ns: the intact membrane, with pHLIP(α-helix) half inserted
Final: 150ns: pHLIP fully in the membrane; Hole formed beside the
pHLIP, as a water channel
Figure 3: number of water molecules in the hole
as a function of time
Figure 4: Minimal cross-sectional area of hole
as a function of time
Conclusion
1.The pHLIP, when half inserted in the membrane, it can insert into the membrane rapidly.
2.In the acidic environment, pHLIP, when inserted in the membrane, can induce the membrane to form a stable water hole, but it cannot mechanically damage the membrane.
3.The results are important to understand the water channel and toxicity of proteins, and it demonstrate the possibility of using PHLIP as a new drug molecular cargo.
References
[1]Yana et al, Energetics of peptide (pHLIP) binding to and folding across a lipid bilayer membrane, PNAS, 105,40,2008
[2]Yana et al, Engleman, Translocation of molecules into cells by pH-dependent insertion of a transmembrane helix, PNAS, 103,17,2006
[3]Pieter E. S. et al, Induction of negative curvature as mechanism of cell toxicity by amyloidogenic peptides, JACS,131(12),4470,2009
-----Thank Yin Luo, Zhaoming Fu, Yan Lu, Huiyu Li, Yun Zhang, Zhongwen Chang for helpful discussion-----