User:Mark Macbeth/Sandbox4: Difference between revisions
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An identical protein, called [http://www.uniprot.org/uniprot/Q9V3V0 X16], was discovered in an earlier paper studying different genes that change expression during [https://en.wikipedia.org/wiki/B_cell B-cell] development<ref name="Corbo2013">PMID:23685143</ref>. At the time, the protein was assumed to play a role in RNA processing and cellular proliferation, a finding that was later proved to be true<ref name="Ayane">PMID:2030943</ref><ref name="Cacero">PMID:11932019</ref>. | An identical protein, called [http://www.uniprot.org/uniprot/Q9V3V0 X16], was discovered in an earlier paper studying different genes that change expression during [https://en.wikipedia.org/wiki/B_cell B-cell] development<ref name="Corbo2013">PMID:23685143</ref>. At the time, the protein was assumed to play a role in RNA processing and cellular proliferation, a finding that was later proved to be true<ref name="Ayane">PMID:2030943</ref><ref name="Cacero">PMID:11932019</ref>. | ||
The SRp20 protein has been shown to play a role in cancer progression and neurological disorders, specifically through alternative splicing. For example, SRp20 has been shown to play a role in alternative splicing of the Tau protein, an integral protein in the progression of Alzheimer’s disease<ref name="Corbo2013">PMID:23685143</ref>. SRp20 has even been found to serve as a splicing factor for its own mRNA, influencing the inclusion of exon 4<ref name="Corbo2013">PMID:23685143</ref>. Another function of SRp20 is its role in export of mRNA out of the nucleus, notably [https://en.wikipedia.org/wiki/Histone_H2A H2A histone] mRNA export<ref name="Hargous">PMID:17036044</ref>. | The SRp20 protein has been shown to play a role in cancer progression and neurological disorders, specifically through alternative splicing. For example, SRp20 has been shown to play a role in alternative splicing of the Tau protein, an integral protein in the progression of Alzheimer’s disease<ref name="Corbo2013">PMID:23685143</ref>. SRp20 has even been found to serve as a splicing factor for its own mRNA, influencing the inclusion of exon 4<ref name="Corbo2013">PMID:23685143</ref>. Another function of SRp20 is its role in export of mRNA out of the nucleus, notably [https://en.wikipedia.org/wiki/Histone_H2A H2A histone] mRNA export<ref name="Hargous">PMID:17036044</ref>. | ||
<StructureSection load='2i2y' size='400' frame='true' side='right' caption='SRp20 bound to RNA ligand (PDB entry [[2i2y]])' scene='78/782597/Rrmredgreen/2'> | |||
= Structure and Function = | = Structure and Function = | ||
Attempts to determine the structure of native SRp20 have been largely unsuccessful due to the low solubility of the protein. This is likely due to the hydrophobic core of the RRM and exposed hydrophobic residues for RNA recognition on the β-sheets. As a solution, researchers removed the SR domain from the C terminus, leaving only the SRp20 RRM and a small arginine rich segment at the C terminus, then fused with a soluble <scene name='78/782597/Imager0/2'>IgG binding domain</scene> of Streptococcal protein G to the N terminus of the protein, providing the first published structure of the SRp20 RRM via NMR. However, the solution of the structure via [https://en.wikipedia.org/wiki/Nuclear_magnetic_resonance NMR], in addition to fusion with a globular tag, results in multiple possible conformations of the protein, meaning measurements such as bond angles, lengths, and substrate interactions are variable. Further, information concerning structural aspects of the SR domain are still limited to experimental data of protein function with certain mutations or deletions, and by comparison to sister proteins such as 9G8. To date, structure of the SR domain or the protein without the globular tag have not been solved, nor has a crystal structure for any part of the protein been determined<ref name="Hargous">PMID:17036044</ref>. | Attempts to determine the structure of native SRp20 have been largely unsuccessful due to the low solubility of the protein. This is likely due to the hydrophobic core of the RRM and exposed hydrophobic residues for RNA recognition on the β-sheets. As a solution, researchers removed the SR domain from the C terminus, leaving only the SRp20 RRM and a small arginine rich segment at the C terminus, then fused with a soluble <scene name='78/782597/Imager0/2'>IgG binding domain</scene> of Streptococcal protein G to the N terminus of the protein, providing the first published structure of the SRp20 RRM via NMR. However, the solution of the structure via [https://en.wikipedia.org/wiki/Nuclear_magnetic_resonance NMR], in addition to fusion with a globular tag, results in multiple possible conformations of the protein, meaning measurements such as bond angles, lengths, and substrate interactions are variable. Further, information concerning structural aspects of the SR domain are still limited to experimental data of protein function with certain mutations or deletions, and by comparison to sister proteins such as 9G8. To date, structure of the SR domain or the protein without the globular tag have not been solved, nor has a crystal structure for any part of the protein been determined<ref name="Hargous">PMID:17036044</ref>. | ||
