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Apolipoproteins are proteins that bind lipids (oil-soluble substances such as fat and cholesterol) to form lipoproteins. They transport lipids (and fat soluble vitamins) in blood, cerebrospinal fluid and lymph.

Apolipoprotein
PDB 1nfn EBI.jpg
apolipoprotein e3 (apoe3)
Identifiers
SymbolApolipoprotein
PfamPF01442
InterProIPR000074
SCOP1oef
SUPERFAMILY1oef
OPM superfamily172
OPM protein3r2p

The lipid components of lipoproteins are insoluble in water. However, because of their detergent-like (amphipathic) properties, apolipoproteins and other amphipathic molecules (such as phospholipids) can surround the lipids, creating a lipoprotein particle that is itself water-soluble, and can thus be carried through water-based circulation (i.e., blood, lymph).

In addition to stabilizing lipoprotein structure and solubilizing the lipid component, apolipoproteins interact with lipoprotein receptors and lipid transport proteins, thereby participating in lipoprotein uptake and clearance. They also serve as enzyme cofactors for specific enzymes involved in the metabolism of lipoproteins.[1]

Apolipoproteins are also exploited by hepatitis C virus (HCV) to enable virus entry, assembly and transmission and also play a role in viral pathogenesis and viral evasion from neutralizing antibodies.[2]

Contents

FunctionsEdit

In lipid transport, apolipoproteins function as structural components of lipoprotein particles, ligands for cell-surface receptors and lipid transport proteins, and cofactors for enzymes (e.g. apolipoprotein C-II for lipoprotein lipase and apolipoprotein A-I (apoA1) for lecithin-cholesterol acyltransferase). Different lipoproteins contain different classes of apolipoproteins and this influences their function. Apoplipoprotein B plays a particularly important role in lipoprotein transport being the primary organizing protein of many lipoproteins.[1] Apolipoprotein A-I (apoA1) is the major structural protein component of high-density lipoproteins (HDL), although it is present in other lipoproteins in smaller amounts.[3] Apolipoprotein A-IV (apoA4) is present in chylomicrons, very-low-density lipoproteins (VLDL) and HDL thought to act primarily in reverse cholesterol transport[4] and intestinal lipid absorption via chylomicron assembly and secretion.[1] Apolipoprotein E (apoE) plays an important role in the transport and uptake of cholesterol by way of its high affinity interaction with lipoprotein receptors, including the low-density lipoprotein (LDL) receptor. Apo E is the major lipoprotein in the central nervous system and has been implicated in dementia and Alzheimer's disease.[5] Recent findings with apoA1 and apoE suggest that the tertiary structures of these two members of the human exchangeable apolipoprotein gene family are related.[6] The three-dimensional structure of the LDL receptor-binding domain of apoE indicates that the protein forms an unusually elongated four-helix bundle that may be stabilised by a tightly packed hydrophobic core that includes leucine zipper-type interactions and by numerous salt bridges on the mostly charged surface. Basic amino acids important for LDL receptor binding are clustered into a surface patch on one long helix.[7]

  • They are enzyme coenzymes
  • Lipid transport proteins
  • Ligands for interaction with lipoprotein receptors in tissues ( apoB100 and apoE for LDL-receptors, apoA-I for HDL receptors)

ClassesEdit

There are multiple classes of apolipoproteins and several sub-classes:

Exchangeable apolipoproteins (apoA, apoC and apoE) have the same genomic structure and are members of a multi-gene family that probably evolved from a common ancestral gene. ApoA1 and ApoA4 are part of the APOA1/C3/A4/A5 gene cluster on chromosome 11.[8]

Hundreds of genetic polymorphisms of the apolipoproteins have been described, and many of them alter their structure and function.

Synthesis and regulationEdit

Apolipoprotein synthesis in the intestine is regulated principally by the fat content of the diet.

Apolipoprotein synthesis in the liver is controlled by a host of factors, including dietary composition, hormones (insulin, glucagon, thyroxin, estrogens, androgens), alcohol intake, and various drugs (statins, niacin, and fibric acids). Apo B is an integral apoprotein whereas the others are peripheral apoproteins.

See alsoEdit

ReferencesEdit

  1. ^ a b c Ramasamy I (December 2014). "Recent advances in physiological lipoprotein metabolism". Clinical Chemistry and Laboratory Medicine. 52 (12): 1695–727. doi:10.1515/cclm-2013-0358. PMID 23940067.
  2. ^ Wrensch F, Crouchet E, Ligat G, Zeisel MB, Keck ZY, Foung SK, Schuster C, Baumert TF (2018). "Hepatitis C Virus (HCV)-Apolipoprotein Interactions and Immune Evasion and Their Impact on HCV Vaccine Design". Frontiers in Immunology. 9: 1436. doi:10.3389/fimmu.2018.01436. PMC 6021501. PMID 29977246.
  3. ^ von Zychlinski A, Williams M, McCormick S, Kleffmann T (June 2014). "Absolute quantification of apolipoproteins and associated proteins on human plasma lipoproteins". Journal of Proteomics. 106: 181–90. doi:10.1016/j.jprot.2014.04.030. PMID 24780726.
  4. ^ Steinmetz A, Barbaras R, Ghalim N, Clavey V, Fruchart JC, Ailhaud G (May 1990). "Human apolipoprotein A-IV binds to apolipoprotein A-I/A-II receptor sites and promotes cholesterol efflux from adipose cells". The Journal of Biological Chemistry. 265 (14): 7859–63. PMID 2159462.
  5. ^ Chang TY, Yamauchi Y, Hasan MT, Chang C (December 2017). "Cellular cholesterol homeostasis and Alzheimer's disease". Journal of Lipid Research. 58 (12): 2239–2254. doi:10.1194/jlr.R075630. PMC 5711498. PMID 28298292.
  6. ^ Saito H, Lund-Katz S, Phillips MC (July 2004). "Contributions of domain structure and lipid interaction to the functionality of exchangeable human apolipoproteins". Progress in Lipid Research. 43 (4): 350–80. doi:10.1016/j.plipres.2004.05.002. PMID 15234552.
  7. ^ Wilson C, Wardell MR, Weisgraber KH, Mahley RW, Agard DA (June 1991). "Three-dimensional structure of the LDL receptor-binding domain of human apolipoprotein E". Science. 252 (5014): 1817–22. Bibcode:1991Sci...252.1817W. doi:10.1126/science.2063194. PMID 2063194.
  8. ^ Fullerton SM, Buchanan AV, Sonpar VA, Taylor SL, Smith JD, Carlson CS, Salomaa V, Stengård JH, Boerwinkle E, Clark AG, Nickerson DA, Weiss KM (June 2004). "The effects of scale: variation in the APOA1/C3/A4/A5 gene cluster". Human Genetics. 115 (1): 36–56. doi:10.1007/s00439-004-1106-x. PMID 15108119.

External linksEdit