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Lipid Membrane Mimetics in Functional and Structural Studies of Integral Membrane Proteins

期刊

MEMBRANES
卷 11, 期 9, 页码 -

出版社

MDPI
DOI: 10.3390/membranes11090685

关键词

integral membrane proteins; lipid membrane mimetics; detergent micelles; bicelles; nanodiscs; liposomes

资金

  1. Department of Chemistry and Biochemistry at TTU

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Integral membrane proteins play crucial roles in cell physiology, but mutations and environmental factors can lead to dysfunctional IMPs. Understanding the mechanisms of IMP function and malfunction at the molecular level is essential for advancing our knowledge of cellular physiology and facilitating pharmaceutical developments. In vitro studies using membrane mimetics provide valuable insights into IMP structure and function dynamics.
Integral membrane proteins (IMPs) fulfill important physiological functions by providing cell-environment, cell-cell and virus-host communication; nutrients intake; export of toxic compounds out of cells; and more. However, some IMPs have obliterated functions due to polypeptide mutations, modifications in membrane properties and/or other environmental factors-resulting in damaged binding to ligands and the adoption of non-physiological conformations that prevent the protein from returning to its physiological state. Thus, elucidating IMPs' mechanisms of function and malfunction at the molecular level is important for enhancing our understanding of cell and organism physiology. This understanding also helps pharmaceutical developments for restoring or inhibiting protein activity. To this end, in vitro studies provide invaluable information about IMPs' structure and the relation between structural dynamics and function. Typically, these studies are conducted on transferred from native membranes to membrane-mimicking nano-platforms (membrane mimetics) purified IMPs. Here, we review the most widely used membrane mimetics in structural and functional studies of IMPs. These membrane mimetics are detergents, liposomes, bicelles, nanodiscs/Lipodisqs, amphipols, and lipidic cubic phases. We also discuss the protocols for IMPs reconstitution in membrane mimetics as well as the applicability of these membrane mimetic-IMP complexes in studies via a variety of biochemical, biophysical, and structural biology techniques.

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