Penetration of HIV-1 Tat47–57 into PC/PE Bilayers Assessed by MD Simulation and X-ray Scattering

Membranes

Chris Neale²  Kun Huang²  Angel E. Garc໚²  Stephanie Tristram-Nagle¹ 

[1] Biological Physics Group, Department of Physics, Carnegie Mellon University, 5000 Forbes Avenue, Pittsburgh, PA 15213, USA;Department of Physics, Applied Physics and Astronomy, Rensselaer Polytechnic Institute, 110 8th St, Troy, NY 12180-3590, USA; E-Mails:

关键词: cell-penetrating peptide;    lipid bilayers;    peptide translocation;    molecular dynamics simulation;    X-ray scattering;    HIV-1 Tat;   

DOI  :  10.3390/membranes5030473

来源: mdpi

【 摘 要 】

The interactions of the basic, cell-penetrating region (Y₄₇GRKKRRQRRR₅₇) of the HIV-1 Tat protein with dioleoylphosphatidylcholine (DOPC) bilayers were previously assessed by comparing experimental X-ray diffuse scattering with atomistic molecular dynamics simulations. Here, we extend this investigation by evaluating the influence of phosphatidylethanolamine (PE) lipids. Using experimental bilayer form factors derivedfrom X-ray diffuse scattering data as a guide, our simulations indicate that Tat peptides localize close to the carbonyl-glycerol group in the headgroup region of bilayers composed of either DOPC or DOPC:DOPE (1:1) lipid. Our results also suggest that Tat peptides may more frequently insert into the hydrophobic core of bilayers composed of PC:PE (1:1) lipids than into bilayers composed entirely of PC lipids. PE lipids may facilitate peptide translocation across a lipid bilayer by stabilizing intermediate states in which hydrated peptides span the bilayer.

【 授权许可】

CC BY   
© 2015 by the authors; licensee MDPI, Basel, Switzerland.