Apolipoprotein
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| apolipoprotein e3 (apoe3) | |||||||||
| Identifiers | |||||||||
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| Symbol | Apolipoprotein | ||||||||
| Pfam | PF01442 | ||||||||
| InterPro | IPR000074 | ||||||||
| SCOP | 1oef | ||||||||
| SUPERFAMILY | 1oef | ||||||||
| OPM family | 193 | ||||||||
| OPM protein | 3r2p | ||||||||
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Apolipoproteins are proteins that bind lipids (oil-soluble substances such as fat and cholesterol) to form lipoproteins and transport the lipids through the lymphatic and circulatory systems.
The lipid components of lipoproteins are not soluble in water; however, because of their detergent-like (amphipathic) properties, apolipoproteins and other amphipathic molecules (such as phospholipids) can surround the lipids, creating the lipoprotein particle that is itself water-soluble, and can thus be carried through water-based circulation (i.e., blood, lymph).
Apolipoproteins also serve as enzyme cofactors, receptor ligands, and lipid transfer carriers that regulate the metabolism of lipoproteins and their uptake in tissues.
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[edit] Functions
Apolipoproteins function in lipid transport as structural components of lipoprotein particles, cofactors for enzymes and ligands for cell-surface receptors. In particular, apoA1 is the major protein component of high-density lipoproteins; apoA4 is thought to act primarily in intestinal lipid absorption; and apoE is a blood plasma protein that mediates the transport and uptake of cholesterol and lipid by way of its high affinity interaction with different cellular receptors, including the low-density lipoprotein (LDL) receptor. Recent findings with apoA1 and apoE suggest that the tertiary structures of these two members of the human exchangeable apolipoprotein gene family are related.[1] 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.[2]
- They are enzyme coenzymes (C-II for lipoprotein lipase and A-I for lecithin-cholesterol acyltransferase)
- Lipid transport proteins
- Ligands for interaction with lipoprotein receptors in tissues ( apoB100 and apoE for LDL-receptors, apoA-I for HDL receptors)
[edit] Classes
There are two major types of apolipoproteins. Apolipoproteins B form low-density lipoprotein ("bad cholesterol") particles. These proteins have mostly beta-sheet structure and associate with lipid droplets irreversibly. Other apolipoproteins form high-density lipoprotein ("good cholesterol") particles. These proteins consist of alpha-helices and associate with lipid droplets reversibly. During binding to the lipid particles these proteins change their three-dimensional structure.
There are six classes of apolipoproteins and several sub-classes:
- A (apo A-I, apo A-II, apo A-IV, and apo A-V)
- B (apo B48 and apo B100)
- C (apo C-I, apo C-II, apo C-III, and apo C-IV)
- D
- E
- H
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.[3]
Hundreds of genetic polymorphisms of the apolipoproteins have been described, and many of them alter their structure and function.
[edit] Synthesis and regulation
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.
[edit] References
- ^ Saito H, Lund-Katz S, Phillips MC (July 2004). "Contributions of domain structure and lipid interaction to the functionality of exchangeable human apolipoproteins". Prog. Lipid Res. 43 (4): 350-80. doi:10.1016/j.plipres.2004.05.002. PMID 15234552.
- ^ 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. PMID 2063194.
- ^ 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". Hum. Genet. 115 (1): 36-56. doi:10.1007/s00439-004-1106-x. PMID 15108119.
[edit] See also
[edit] External links
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This article incorporates text from the public domain Pfam and InterPro IPR000074
