Interaction mechanism between proteins and lipid membranes characterized by vacuum-ultraviolet circular dichroism spectroscopy

概要

Interaction between peripheral membrane protein and lipid membrane plays a
crucial role in the biological functions such as drug delivery into the membrane (or
cell), formation of myelin membrane around neuron cell, and membrane disruption
related to immune system1–3. The interaction also induces the formation of toxic
oligomers of amyloidogenic proteins, leading to serious neurological diseases such
as Alzheimer’s disease and Parkinson’s disease4. It is known that the water-soluble
protein approaches to and interacts with the surface of membrane to induce large
structural changes accompanying the expression of its functions or diseases1–4. To
gain detailed insight into the molecular mechanisms underlying the life phenomena,
it is therefore of great importance to understand the complex nature of the
interactions between proteins and lipid membranes, including the structural change
of the proteins.
X-ray crystallography, nuclear magnetic resonance (NMR) spectroscopy, and
cryogenic electron microscopy (cryo-EM) are most important methods for
characterizing the secondary and tertiary structures of proteins. Although X-ray
crystallography requires the crystallization of proteins, with the developments for
membrane protein crystallization techniques5, this method has become possible for
many integral membrane proteins. As for NMR spectroscopy, the targets are
restricted to the proteins with low molecular weight (upper limit: 30 kDa), but the
development of new types of membrane mimetic model (e.g., nanodisc) has made
it possible to analyze the structure of several membrane-bound peptides under
membrane mimetic condition6. Cryo-EM is a recent emerging technique that can
be used to analyze the structure of isolated biomolecular complexes with molecular
weight ranging from tens of kilo-Daltons (e.g., hemoglobin) to several megaDaltons (e.g., virus particles)7. With recent advances in detector and image
processing technologies7, cryo-EM has been applied to structural analysis of
various membrane proteins, including those even in the presence of liposomes8
that have the characteristics of real cell membrane. ...

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