Abstract
Membrane proteins can be classified into two main categories—integral and peripheral membrane proteins—depending on the nature of their membrane interaction. Peripheral membrane proteins are highly unique amphipathic proteins that interact with the membrane indirectly, using electrostatic or hydrophobic interactions, or directly, using hydrophobic tails or GPI-anchors. The nature of this interaction not only influences the location of the protein in the cell, but also the function. In addition to their unique relationship with the cell membrane, peripheral membrane proteins often play a key role in the development of human diseases such as African sleeping sickness, cancer, and atherosclerosis. This review will discuss the membrane interaction and role of periplasmic nitrate reductase, CymA, cytochrome c, alkaline phosphatase, ecto-5’-nucleotidase, acetylcholinesterase, alternative oxidase, type-II NADH dehydrogenase, and dihydroorotate dehydrogenase in certain diseases. The study of these proteins will give new insights into their function and structure, and may ultimately lead to ground-breaking advances in the treatment of severe diseases.
Highlights
The lipid membrane surrounding cells and their compartments hosts proteins that perform functions essential for both cell physiology and disease progression
Using ribonucleotide reductase as a basis for the Andersson and Nordlund model, they observed that two conserved residues, Q247 and Y258, exist in a crevice leading from a hydrophobic region towards the diiron center between α helices 2 and 3 of the Alternative oxidases (AOXs) [82,83]
Peripheral membrane proteins (PMPs) are a highly diverse group of proteins that can interact with the phospholipid bilayer in unique ways: through direct binding using hydrophobic alpha helices or GPI anchors, or indirect binding using electrostatic and hydrophobic interactions
Summary
The lipid membrane surrounding cells and their compartments hosts proteins that perform functions essential for both cell physiology and disease progression. PMPs play a key role in metabolic pathways, making themplay attractive propositions lipid embedded in the membrane, and quinone oxidoreductases, which a key role in in the search for cures for diseases ranging from tuberculosis [13] and cancer [14,15,16,17,18] to the electron transportparasitic chains of both oxidative phosphorylation and photosynthesis, as infections [19] Their highly amphipathic nature and their dependence both pathways use quinones as their is electron. This results in intense debate surrounding the mechanism of action or structure of many PMPs, leading to controversies in the field as in the case of type-II NADH dehydrogenases [21] In this particular example, one active site is within the hydrophobic membrane interior while the other is in solution [21]. Inhibits cancer progression; 9,900,000 total cancer deaths/year [42]
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