Rett Syndrome Protein: Difference between revisions
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==Rett Syndrome Protein== | ==Rett Syndrome Protein== | ||
<StructureSection load | <StructureSection load='1stp' size='340' side='right' caption='Caption for this structure' scene=''> | ||
This is a default text for your page '''Rett Syndrome Protein'''. Click above on '''edit this page''' to modify. Be careful with the < and > signs. | This is a default text for your page '''Rett Syndrome Protein'''. Click above on '''edit this page''' to modify. Be careful with the < and > signs. | ||
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. | 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. | ||
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=='''Structure'''== | =='''Structure'''== | ||
The MeCP2 DNA Binding Domain binds to methylated BDNF DNA sequence primarily using hydrophobic pockets. It is able to recognize mCpG DNA by noticing 5 unique CH-O hydrogen bonds within water molecules. An example is how water-24 forms hydrogen bonds with Try 123, Arg 133, water 22, and m5C8. Compared to water-22 which forms hydrogen bonds with | The MeCP2 DNA Binding Domain binds to methylated BDNF DNA sequence primarily using hydrophobic pockets. It is able to recognize mCpG DNA by noticing 5 unique CH-O hydrogen bonds within water molecules. An example is how water-24 forms hydrogen bonds with Try 123, Arg 133, water 22, and m5C8. Compared to water-22 which forms hydrogen bonds with Asp 121, waster-24, water-21, and N4 of m5C33. Only Asp 121 direct interacts with the DNA bases. It forms hydrogen bonds with methyl groups with Arg which are stabilized with salt bridges. | ||
The entire strand is comprised of 51% β-sheet, 10% α-helix, and almost 40% unstructured. The terminal carbon region contains a rare tandem ASX-ST motif which includes an | The entire strand is comprised of 51% β-sheet, 10% α-helix, and almost 40% unstructured. The terminal carbon region contains a rare tandem ASX-ST motif which includes an ASX turn proceeded by an ST motif. This unique turn is stabilized with hydrogen bond interactions connecting the nitrogens between amino acids. These finds are consistent as typically MeCP2 behaves as a monomer while in ionic conditions and molar concentrations, and had an unusually low sedimentation coefficient (2.2 S) and a correspondingly high frictional coefficient ratio (f/fo = 2.4). This proves the helical structure. | ||
MeCP2 is comprised of six biochemically distinct domains which are located at the N-terminus. It includes HMGD1, MBD, HMGD2, TRD, carboxyl terminal domain (CTD)-α, and CTD-β from the amino to carboxyl terminals. Some of these site are rapidly digested by Trypsin while others are restricted. The two more important for the protein’s function include MBD which is selectively binds 5MeCyt and the other is TRD which binds cofactors attracting histone deacetylase and leads to transcription repression. In addition, MBD is the only structured domain. The MBD domain contains the most common missense mutation causing Rett Syndrome when there is a change in the ASX-ST motif. This minor alteration inhibits the binding of DNA. This topic will be further discussed later in the literature. <ref name="One">Marchetto M, Carromeu C, Acab A, et al. A Model for Neural Development and Treatment of Rett Syndrome Using Human Induced Pluripotent Stem Cells. Science Direct . https://www.sciencedirect.com/science/article/pii/S0092867410011864?via=ihub. Published November 12, 2010. Accessed March 10, 2019.</ref> <ref name="Hite">Hite KC, Adams VH, Hansen JC. Recent advances in MeCP2 structure and function. Biochemistry and cell biology = Biochimie et biologie cellulaire. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2874317/. Published February 2009. Accessed March 7, 2019.</ref> <ref name="War">Warby S. Discovery of a new protein isoform of MeCP2 and exon 1 mutations causing Rett syndrome. HotSpots.:108-110. https://maryville.illiad.oclc.org/illiad/pdf/157498.pdf. Accessed March 7, 2019.</ref> | MeCP2 is comprised of six biochemically distinct domains which are located at the N-terminus. It includes HMGD1, MBD, HMGD2, TRD, carboxyl terminal domain (CTD)-α, and CTD-β from the amino to carboxyl terminals. Some of these site are rapidly digested by Trypsin while others are restricted. The two more important for the protein’s function include MBD which is selectively binds 5MeCyt and the other is TRD which binds cofactors attracting histone deacetylase and leads to transcription repression. In addition, MBD is the only structured domain. The MBD domain contains the most common missense mutation causing Rett Syndrome when there is a change in the ASX-ST motif. This minor alteration inhibits the binding of DNA. This topic will be further discussed later in the literature. <ref name="One">Marchetto M, Carromeu C, Acab A, et al. A Model for Neural Development and Treatment of Rett Syndrome Using Human Induced Pluripotent Stem Cells. Science Direct . https://www.sciencedirect.com/science/article/pii/S0092867410011864?via=ihub. Published November 12, 2010. Accessed March 10, 2019.</ref> <ref name="Hite">Hite KC, Adams VH, Hansen JC. Recent advances in MeCP2 structure and function. Biochemistry and cell biology = Biochimie et biologie cellulaire. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2874317/. Published February 2009. Accessed March 7, 2019.</ref> <ref name="War">Warby S. Discovery of a new protein isoform of MeCP2 and exon 1 mutations causing Rett syndrome. HotSpots.:108-110. https://maryville.illiad.oclc.org/illiad/pdf/157498.pdf. Accessed March 7, 2019.</ref> | ||
