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Structure Determination of HIV-1 Tat/Fluid Phase Membranes and DMPC Ripple Phase Using X-Ray Scattering (Hardcover, 1st ed. 2015)
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Structure Determination of HIV-1 Tat/Fluid Phase Membranes and DMPC Ripple Phase Using X-Ray Scattering (Hardcover, 1st ed. 2015)
Series: Springer Theses
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This Thesis in biological physics has two components, describing
the use of X-ray scattering techniques to study the structure of
two different stacked lipid membrane systems. The first part
focuses on the interaction between a short 11-mer peptide, Tat,
which is part of the Tat protein in the HIV-1 virus. Although
highly positively charged, the Tat protein has been shown to
translocate through hydrocarbon lipid bilayers easily, without
requiring the cell's energy, which is counter to its Born
self-energy. In this work Tat's location in the headgroup region
was demonstrated using a combined X-ray scattering and molecular
dynamics approach. Bilayer thinning was observed as well as
softening of different membrane mimics due to Tat. It was concluded
that Tat's headgroup location, which increases the area/lipid, and
its bilayer softening likely reduce the energy barrier for passive
translocation. The second part is a rigorous investigation of an
enigmatic phase in the phase diagram of the lipid
dimyristoylphosphatidylcholine (DMPC). The ripple phase has
fascinated many researchers in condensed matter physics and
physical chemistry as an example of periodically modulated phases,
with many theoretical and simulation papers published. Despite
systematic studies over the past three decades, molecular details
of the structure were still lacking. By obtaining the highest
resolution X-ray data so far, this work revealed the complex nature
of the chain packing, as well as confirming that the major side is
thicker than the minor side of the saw-tooth ripple structure. The
new model shows that the chains in the major arm are tilted with
respect to the bilayer normal and that the chains in the minor arm
are slightly more disordered than all-trans gel-phase chains, i.e.,
the chains in the minor arm are more fluid-like. This work provides
the highest resolution X-ray structure of the ripple phase to-date.
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