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=Protein Phosphatase 2A= | __NOTOC__=Protein Phosphatase 2A= | ||
Protein | Protein Phosphatases are general class of enzymes that are responsible for dephosphorylating other molecules or proteins. A kinase enzyme could attach a phosphate group while the phosphatases could remove the group. The process of phosphorylation occurs in many metabolic processes and are one of the most common post transcriptional modifications. Protein phosphatases typically use three different amino acids to phosphorylate a protein. The three most common are serine, threonine and tyrosine. Protein phosphatase 2A uses serine and threonine to phosphorylate a compound. Protein Phosphatases are involved in many biological pathways. This is due to the fact that they have broad substrate specificity. Protein phosphatases are involved in process such as cell-cycle regulation, cell growth and cell development. Protein phosphatases are also involved in signal transduction and can be involved with the phosphorylation of signal proteins such as Raf and MEK. | ||
<ref>Bradford D. "Protein Phosphatases." Current opinions in structural biology (1995): 728-734.</ref> The function and mechanisms of protein phosphatase is unclear to the present date. PP2A is a three subunit holoenzyme that features a HEAT repeat, '''H'''untington-'''e'''longation-'''A''' subunit-'''T'''OR, which is also found in the [http://en.wikipedia.org/wiki/Huntingtin/ huntingtin gene]. The following sections will discuss the PP2A enzyme and the importance of understanding HEAT repeats. | |||
<Structure load='2NPP' size='400' frame='true' align='right' caption='Protein Phosphatase 2A' scene='69/691537/Starter/1' /> | <Structure load='2NPP' size='400' frame='true' align='right' caption='Protein Phosphatase 2A' scene='69/691537/Starter/1' /> | ||
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== HEAT Repeat Motif == | == HEAT Repeat Motif == | ||
PP2A belongs in the HEAT Repeat Motif or | PP2A belongs in the HEAT Repeat Motif or '''H'''untington-'''e'''longation-'''A''' subunit-'''T'''OR. The main backbone of PP2A is 15 repeating units or <scene name='69/691537/Heat/1'>HEAT units</scene>, each composed of a conserved 39-residue sequence.The HEAT Motif has a signature sequence of conserved residues asparagine at position 19 and arginine at position 25. Each HEAT unit consists of a pair of antiparallel alpha-helices. These antiparallel helices assemble in a L-shaped fashion resulting in an overall shape of a double layer of alpha helices. These HEAT units are responsible for a majority of the overall protein packing and structure by interactions of the ridges of each HEAT unit. <ref>PMID: 9989501</ref> | ||
== Huntington's Disease == | == Huntington's Disease == | ||
One unique feature of the Huntington's Disease protein, Htt, is that it features a HEAT repeat like that of PP2A. Continued understanding of how PP2A heat repeat operates could provide valuable insight in understanding the mechanisms of Huntington's Disease function. Huntington's Disease is caused by the huntingin protein, Htt, which is found in all mammalian cells. The protein is known to be involved with numerous functions in the body such as signal transduction, transcription and intercellular transporting. <ref>Harjes P, Wanker EE (2003). "The hunt for huntingtin function: interaction partners tell many different stories". Trends Biochem. Sci. 28 (8): 425–33. doi:10.1016/S0968-0004(03)00168-3</ref> Huntington's Disease is thought to be a result of toxic function of the Htt protein, mHtt, instead of a lack or excess of the protein. <ref>Walker FO (2007). "Huntington's disease". Lancet 369 (9557): 218–28 [221]. doi:10.1016/S0140-6736(07)60111-1</ref> Modifications of the Htt protein result in either mHtt proteins high in glutamine or protein fragments from cleavage that are high in glutamine. Glutamine is plentiful in the mHtt protein due to the fact that it is coded for by the cytosine-adenine-guanine series in the HTT gene that is expanded in the mutation. The polar nature of glutamine causes the protein to form clumps which center around the axons and dendrites of neurons. These clumps result in lack of normal nerve function leading to the visible symptoms of Huntington's Disease. <ref>"Huntingtin Protein and Protein Aggregation | HOPES – A guide to the science of Huntington's disease"</ref> The following [http://commons.wikimedia.org/wiki/File:Neuron_with_mHTT_inclusion_zoomed.jpg | One unique feature of the Huntington's Disease protein, Htt, is that it features a HEAT repeat like that of PP2A. Continued understanding of how PP2A heat repeat operates could provide valuable insight in understanding the mechanisms of Huntington's Disease function. Huntington's Disease is caused by the huntingin protein, Htt, which is found in all mammalian cells. The protein is known to be involved with numerous functions in the body such as signal transduction, transcription and intercellular transporting. <ref>Harjes P, Wanker EE (2003). "The hunt for huntingtin function: interaction partners tell many different stories". Trends Biochem. Sci. 28 (8): 425–33. doi:10.1016/S0968-0004(03)00168-3</ref> Huntington's Disease is thought to be a result of toxic function of the Htt protein, mHtt, instead of a lack or excess of the protein. <ref>Walker FO (2007). "Huntington's disease". Lancet 369 (9557): 218–28 [221]. doi:10.1016/S0140-6736(07)60111-1</ref> Modifications of the Htt protein result in either mHtt proteins high in glutamine or protein fragments from cleavage that are high in glutamine. Glutamine is plentiful in the mHtt protein due to the fact that it is coded for by the cytosine-adenine-guanine series in the HTT gene that is expanded in the mutation. The polar nature of glutamine causes the protein to form clumps which center around the axons and dendrites of neurons. These clumps result in lack of normal nerve function leading to the visible symptoms of Huntington's Disease. <ref>"Huntingtin Protein and Protein Aggregation | HOPES – A guide to the science of Huntington's disease"</ref> The following [http://commons.wikimedia.org/wiki/File:Neuron_with_mHTT_inclusion_zoomed.jpg link] will provide an image of a neuron that is affected by mHtt. | ||
Huntington's Disease is a genetically inherited disease that is dominant in nature. This means an infected parent will have a 50% chance of transmission to their child. It is classified as a neurodegenerative disorder that will result in death. The disease can strike as early as childhood but usually starts to affect the individual from 35 to 45 years of age. Initial signs consist of mood changes for the first few years followed by disruption of motor skills called chorea. Chorea is a term to describe jerky uncontrolled movements of the extremities followed by the entire body as the disease progresses. Chorea like conditions are also present in individuals with Parkinson's Disease. Huntington's Disease continues to affect the mind as well as the body. The later stages of the disease will result in a individual that could be described as being schizophrenic with dementia and Alzheimer's disease that also has Parkinson's Disease. The individual will fade both mentally and physically until death comes in the common form of heart failure or pneumonia from the weakened condition. This disease creates a lot of controversy in the genetic counseling community due to the fact that it can now be detected as early as in-vitro fertilization. The ramifications from a positive diagnosis would be considered by most as a life shattering event. There is a quote from a Campbell biology textbook that poses the question of 'At what point would it be beneficial to know that the individual has a incurable fatal disease that will generally result in death in the early fifties'? | Huntington's Disease is a genetically inherited disease that is dominant in nature. This means an infected parent will have a 50% chance of transmission to their child. It is classified as a neurodegenerative disorder that will result in death. The disease can strike as early as childhood but usually starts to affect the individual from 35 to 45 years of age. Initial signs consist of mood changes for the first few years followed by disruption of motor skills called chorea. Chorea is a term to describe jerky uncontrolled movements of the extremities followed by the entire body as the disease progresses. Chorea like conditions are also present in individuals with Parkinson's Disease. Huntington's Disease continues to affect the mind as well as the body. The later stages of the disease will result in a individual that could be described as being schizophrenic with dementia and Alzheimer's disease that also has Parkinson's Disease. The individual will fade both mentally and physically until death comes in the common form of heart failure or pneumonia from the weakened condition. This disease creates a lot of controversy in the genetic counseling community due to the fact that it can now be detected as early as in-vitro fertilization. The ramifications from a positive diagnosis would be considered by most as a life shattering event. There is a quote from a Campbell biology textbook that poses the question of 'At what point would it be beneficial to know that the individual has a incurable fatal disease that will generally result in death in the early fifties'? | ||
