|
|
| Line 1: |
Line 1: |
| - | =Apolipoprotein A-I= | + | ==Name of your Protein== |
| - | ==Structure==
| + | <StructureSection load='3VEV' size='340' side='right' caption='Caption for this structure' scene=''> |
| - | <StructureSection load='1av1' size='340' side='right' caption='Apolipoprotein A-I' scene=''> | + | This is a default text for your page. Click above on '''edit this page''' to modify. Be careful with the < and > signs. |
| - | Apolipoproteins are proteins that coat lipoprotein surface that binds lipids such as cholesterol, low-density lipoprotein (LDL), or high-density lipoproteins (HDL) in lipid metabolism. They function in the transport of such lipids in their structure that acts as a ligand to cell receptors and lipid transport proteins. <ref> Voet, D., Voet, J. G., & Pratt, C. W. (2016). Fundamentals of Biochemistry (5th ed.). Hoboken, NJ: John Wiley & Sons.</ref> They are important in the binding and transportation of lipids throughout the body, necessary in energy structural components, and nutrients.
| + | You may include any references to papers as in: the use of JSmol in Proteopedia <ref>DOI 10.1002/ijch.201300024</ref> or to the article describing Jmol <ref>PMID:21638687</ref> to the rescue. |
| - | Apolipoprotein A-I is a protein of APOA1 gene located on the 11th chromosome found in humans that is a component of HDL. Gene for APOA1 protein contains a total of 4 exons that is synthesized for the protein, used in lipid metabolism of HDL. <ref> APOA1 gene: MedlinePlus Genetics. (2020, August 18). Retrieved October 26, 2020, from https://medlineplus.gov/genetics/gene/apoa1/</ref>
| + | |
| - | Apolipoprotein a-1 (apoA-I) is a fairly small molecule that consists of a total of 243 residues and is 29-kD polypeptide in size. Structure in <scene name='75/752268/Color/10'>color</scene> is shown in rainbow, in arrangement from N-terminus (red) of amine group to C-terminus (dark blue) end of carboxyl group.
| + | |
| | == Function == | | == Function == |
| - | Apolipoprotein A-I is responsible in the reverse transport of cholesterol to the liver. It contains amphipathic structure sequences of helices in its repeating <scene name='75/752268/Polar/1'> polar </scene>hydrophilic and non-polar hydrophobic groups that form helices are what allows the interaction between hydrophobic properties of water, such as in the blood stream and hydrophobic lipids. | |
| | | | |
| - | Apolipoprotein A-I is a protein APOA1 gene in humans that is a component of HDL, which a form of good cholesterol in human's diet, used in the transport of cholesterol and phospholipids in the body through the bloodstream in the reverse transport of cholesterol from the tissues to the liver of hepatocytes. They promote cholesterol efflux, a pathway in transferring intracellular cholesterol to extracellular acceptors, from tissues and act as a cofactor for the lecithin cholesterol acyltransferase (LCAT).<ref>Yano, K., Ohkawa, R., Sato, M., Yoshimoto, A., Ichimura, N., Kameda, T., . . . Tozuka, M. (2016, November 09). Cholesterol Efflux Capacity of Apolipoprotein A-I Varies with the Extent of Differentiation and Foam Cell Formation of THP-1 Cells. Retrieved November 14, 2020, from https://www.hindawi.com/journals/jl/2016/9891316/</ref>
| + | == Disease == |
| - | == Clinical significance == | + | |
| - | Apolipoprotein A-1 is found to be as an indicator for cardiovascular disease and atherosclerotic cardiovascular disease. Since APOA1 is a component of HDL associated with good form of cholesterol, when ABOAB (apolipoprotein B) a component of LDL, a form of bad cholesterol levels are elevated in blood can signal as a risk factor for development in hardening of arterial walls and blockage. <ref> Test ID: APOAB Apolipoprotein A1 and B, Serum. (n.d.). Retrieved November 14, 2020, from Test ID: APOAB Apolipoprotein A1 and B, Serum. (n.d.). Retrieved November 14, 2020, from Test ID: APOAB Apolipoprotein A1 and B, Serum</ref> High-density lipoprotein complex is important in the clearing of fats through absorption of cholesterol that is transported into the liver where it is synthesized into bile salts or excreted.<ref> LDL & HDL: Good & Bad Cholesterol. (2020, January 31). Retrieved November 14, 2020, from https://www.cdc.gov/cholesterol/ldl_hdl.htm</ref><ref>Cohen, D. (2008, April). Balancing cholesterol synthesis and absorption in the gastrointestinal tract. Retrieved November 14, 2020, from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2390860/</ref>
| + | |
| | | | |
| - | '''Apolipoprotein A-I (Milano)''' is a mutant form of apolipoprotein A-I associated in reducing coronary artery disease to those genetically predisposition. <ref>CR;, C. (n.d.). Apolipoprotein A-I(Milano): Current perspectives. Retrieved November 14, 2020, from https://pubmed.ncbi.nlm.nih.gov/12642784/</ref> Mutation Milano was first discovered in from a patient in Limone sul Garda, Northern Italy or alarming elevated triglycerides and low HDL with no signs of atherosclerosis or cardiovascular disease. Mutation occurs at 173 residue of <scene name='75/752268/Milano/1'>arginine</scene> replaced with cysteine. <ref>Lowe, D. (2016, November 16). The Long Saga of Apo-A1 Milano. Retrieved November 14, 2020, from https://blogs.sciencemag.org/pipeline/archives/2016/11/16/the-long-saga-of-apo-a1-milano</ref>
| + | == Relevance == |
| - | | + | |
| - | == Diseases == | + | |
| - | '''Tangier disease'''
| + | |
| - | | + | |
| - | Genetic disorder with significantly reduced HDL in the blood caused by mutation of APOA1 gene (ABCA1) caused by abnormal pre-mRNA spicing, in the loss of 22 amino acids of premature stop codon.<ref>Maranghi, M., Truglio, G., Gallo, A., Grieco, E., Verrienti, A., Montali, A., . . . Lucarelli, M. (2018, November 30). A novel splicing mutation in the ABCA1 gene, causing Tangier disease and familial HDL deficiency in a large family. Retrieved November 14, 2020, from https://www.sciencedirect.com/science/article/pii/S0006291X18324781</ref> As a result of decreased apolipoprotein A-1 synthesized, cells undergo large lipid fluxes and accumulated cholesterol and fats. Accumulation of cholesterol in cell due to lack of transport is toxic and impairs cell function. Visible signs of the disease include yellow-orange tonsils and formation of foam cells of lipid-laden macrophages.<ref>McConnell, J. (2019, January 17). Tangier Disease. Retrieved November 15, 2020, from https://www.cancertherapyadvisor.com/home/decision-support-in-medicine/labmed/tangier-disease/</ref>
| + | |
| - | | + | |
| - | '''Amyloidosis'''
| + | |
| - | | + | |
| - | Rare disease caused from abnormal protein amyloid is built up in areas of the heart, kidneys, liver, and other organs. Amyloid, not normally found in the body, is produced from mutation of APOA1 gene that can be caused by 13 of 50 known variants of apolipoprotein A-1 gene between residues 50 to 93 and 170 to 178. Three of mutations are known to cause gene variations that lead to two different frameshifts at amino acids asparagine and alanine (p.Asn74fs and p.Ala154fs) and single amino acid exchange (p.Leu170Pro). <ref>Eriksson, M., Schönland, S., Yumlu, S., Hegenbart, U., Von Hutten, H., Gioeva, Z., . . . Röcken, C. (2009, May). Hereditary apolipoprotein AI-associated amyloidosis in surgical pathology specimens: Identification of three novel mutations in the APOA1 gene. Retrieved November 15, 2020, from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2671344/</ref>
| + | |
| - | Symptoms of amyloidosis is not evident until disease is more progressed. Range of symptoms are also dependent on organ(s) effected that include swelling in legs and ankles, enlarged tongue, shortness of breath, and/or skin conditions such as patches from easily bruising. <ref>Amyloidosis. (2020, March 14). Retrieved November 15, 2020, from https://www.mayoclinic.org/diseases-conditions/amyloidosis/symptoms-causes/syc-20353178</ref>
| + | |
| - | | + | |
| - | '''Alzheimer’s'''
| + | |
| - | | + | |
| - | While apolipoprotein A-1 and alzheimer's is not fully understood, relationship between apolipoprotein A-I and alzheimer's effidence is supported in lower APOA1 levels and HDL in patients with alzheimer's and dementia. Aβ aggregation in Alzheimer’s disease, a form of amyloidoses found in the brain. Association of amyloid-beta (Aβ) aggregates is likely caused by mutations of APOA1 in amyloid formation that enters the brain in cause development of progressive alzheimer's disease in the brain's connection cells that degenerate and die off.<ref>Stoye, N., Jung, P., Guilherme, M., Lotz, J., Fellgiebel, A., & Endres, K. (2020, February 4). Apolipoprotein A1 in Cerebrospinal Fluid Is Insufficient to Distinguish Alzheimer's Disease from Other Dementias in a Naturalistic, Clinical Setting. Retrieved November 15, 2020, from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7081088/</ref>
| + | |
| | | | |
| | == Structural highlights == | | == Structural highlights == |
| | | | |
| - | Apolipoprotein a-1 (apoA-I) is a fairly small molecule that consists of a total of 243 residues and is 29-kD polypeptide in size. Its structure consists of two helical domains that include a four-helix of antiparallel bundle by N terminal and two helix bundle at the C terminal end. ApoA-I consists of <scene name='75/752268/Chains/1'>four chains</scene> alpha helices including chain A (orange), B (blue), C (red), and D (green) as displayed, in which an infinity like structure. C terminal domain of carboxyl group is known to participate in role in lipid binding for transport, found following between residues <scene name='75/752268/Cterm_binding/1'>(190-243).</scene> At the central region, two antiparallel helices form a flexible domain of connected bundles of each end of helices.<ref>And, X. (2011, November 04). Crystal Structure of C-terminal Truncated Apolipoprotein A-I Reveals the Assembly of High Density Lipoprotein (HDL) by Dimerization. Retrieved November 14, 2020, from https://www.jbc.org/content/286/44/38570.abstract?sid=eee11503-e692-438c-a298-52d329852b25</ref>
| + | This is a sample scene created with SAT to <scene name="/12/3456/Sample/1">color</scene> by Group, and another to make <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes. |
| - | | + | |
| - | Apolipoprotein a-1 in the monomer form <scene name='75/752268/Truncated/4'>truncated</scene> (lacking 1-43 residues) consists of unique pseudo-continuous alpha helix highlighted by kinks at <scene name='75/752268/Truncated/3'>Pro residues</scene>, spaced approximately every 22 residues.<ref>Nagao, K., Hata, M., Tanaka, K., Takechi, Y., Nguyen, D., Dhanasekaran, P., . . . Saito, H. (2014, January). The roles of C-terminal helices of human apolipoprotein A-I in formation of high-density lipoprotein particles. Retrieved November 14, 2020, from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3863607/</ref>
| + | |
| - | | + | |
| - | Biomarkers of coronary artery disease are also found to be of modification at glutamate residue 243 of truncated APOA1 of single amino acid.
| + | |
| | | | |
| | </StructureSection> | | </StructureSection> |
| | == References == | | == References == |
| - | 1. Voet, D., Voet, J. G., & Pratt, C. W. (2016). Fundamentals of Biochemistry (5th ed.). Hoboken, NJ: John Wiley & Sons.<references/>
| + | <references/> |
| - | | + | |
| - | 2. APOA1 gene: MedlinePlus Genetics. (2020, August 18). Retrieved October 26, 2020, from https://medlineplus.gov/genetics/gene/apoa1/<references/>
| + | |
| - | | + | |
| - | 3. Mangaraj, M., Nanda, R., & Panda, S. (2016, July). Apolipoprotein A-I: A Molecule of Diverse Function. Retrieved November 04, 2020, from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4910842<references/>
| + | |
| - | | + | |
| - | 4. Yano, K., Ohkawa, R., Sato, M., Yoshimoto, A., Ichimura, N., Kameda, T., . . . Tozuka, M. (2016, November 09). Cholesterol Efflux Capacity of Apolipoprotein A-I Varies with the Extent of Differentiation and Foam Cell Formation of THP-1 Cells. Retrieved November 14, 2020, from https://www.hindawi.com/journals/jl/2016/9891316/<references/>
| + | |
| - | | + | |
| - | 5. Test ID: APOAB Apolipoprotein A1 and B, Serum. (n.d.). Retrieved November 14, 2020, from Test ID: APOAB Apolipoprotein A1 and B, Serum. (n.d.). Retrieved November 14, 2020, from Test ID: APOAB Apolipoprotein A1 and B, Serum<references/>
| + | |
| - | | + | |
| - | 6. LDL & HDL: Good & Bad Cholesterol. (2020, January 31). Retrieved November 14, 2020, from https://www.cdc.gov/cholesterol/ldl_hdl.htm<references/>
| + | |
| - | | + | |
| - | 7. Cohen, D. (2008, April). Balancing cholesterol synthesis and absorption in the gastrointestinal tract. Retrieved November 14, 2020, from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2390860/<references/>
| + | |
| - | | + | |
| - | 8. CR;, C. (n.d.). Apolipoprotein A-I(Milano): Current perspectives. Retrieved November 14, 2020, from https://pubmed.ncbi.nlm.nih.gov/12642784/<references/>
| + | |
| - | | + | |
| - | 9. Lowe, D. (2016, November 16). The Long Saga of Apo-A1 Milano. Retrieved November 14, 2020, from https://blogs.sciencemag.org/pipeline/archives/2016/11/16/the-long-saga-of-apo-a1-milano <references/>
| + | |
| - | | + | |
| - | 10. Nagao, K., Hata, M., Tanaka, K., Takechi, Y., Nguyen, D., Dhanasekaran, P., . . . Saito, H. (2014, January). The roles of C-terminal helices of human apolipoprotein A-I in formation of high-density lipoprotein particles. Retrieved November 14, 2020, from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3863607/<references/>
| + | |
| - | | + | |
| - | 11. And, X. (2011, November 04). Crystal Structure of C-terminal Truncated Apolipoprotein A-I Reveals the Assembly of High Density Lipoprotein (HDL) by Dimerization. Retrieved November 14, 2020, from https://www.jbc.org/content/286/44/38570.abstract?sid=eee11503-e692-438c-a298-52d329852b25<references/>
| + | |
| - | | + | |
| - | 12. Maranghi, M., Truglio, G., Gallo, A., Grieco, E., Verrienti, A., Montali, A., . . . Lucarelli, M. (2018, November 30). A novel splicing mutation in the ABCA1 gene, causing Tangier disease and familial HDL deficiency in a large family. Retrieved November 14, 2020, from https://www.sciencedirect.com/science/article/pii/S0006291X18324781<references/>
| + | |
| - | | + | |
| - | 13. McConnell, J. (2019, January 17). Tangier Disease. Retrieved November 15, 2020, from https://www.cancertherapyadvisor.com/home/decision-support-in-medicine/labmed/tangier-disease/<references/>
| + | |
| - | | + | |
| - | 14. Eriksson, M., Schönland, S., Yumlu, S., Hegenbart, U., Von Hutten, H., Gioeva, Z., . . . Röcken, C. (2009, May). Hereditary apolipoprotein AI-associated amyloidosis in surgical pathology specimens: Identification of three novel mutations in the APOA1 gene. Retrieved November 15, 2020, from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2671344/<references/>
| + | |
| - | | + | |
| - | 15.Amyloidosis. (2020, March 14). Retrieved November 15, 2020, from https://www.mayoclinic.org/diseases-conditions/amyloidosis/symptoms-causes/syc-20353178<references/>
| + | |
| - | | + | |
| - | 16. Stoye, N., Jung, P., Guilherme, M., Lotz, J., Fellgiebel, A., & Endres, K. (2020, February 4). Apolipoprotein A1 in Cerebrospinal Fluid Is Insufficient to Distinguish Alzheimer's Disease from Other Dementias in a Naturalistic, Clinical Setting. Retrieved November 15, 2020, from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7081088/<references/>
| + | |
