User:Alexis Neyman/Sandbox 1

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=== RNA Interactions ===
=== RNA Interactions ===
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1H-15N HSQC results showed a large hydrophobic β-sheet on the RRM binding to the RNA with all four bases interacting with one of the four aromatic residues via hydrophobic interactions <ref name="Hargous">PMID:17036044</ref>. [https://en.wikipedia.org/wiki/Beta_hairpin β-hairpin] amino acids are hydrogen bonded to bases on nucleic acid targets <ref name="Clery">PMID:18515081</ref>. This suggests that the β-hairpin plays a role in SRp20 selectivity for specific ligands. The researchers used a smaller peptide chain to reduce the NMR broadening seen with longer peptides (allowing for structure determination), with the consequence of reduced binding affinity. The ligand used was <scene name='78/781963/Looking_at_the_ligand/1'>CAUC</scene>. The conformation of U3 and C4 shows that U3 bulges out while C4 partially stacks over A2. Interactions with the RRM that the researchers saw were that <scene name='78/781963/C1_and_tyr_13/3'>C1 stacks with Tyr 13</scene> in β1 and <scene name='78/781963/A2_phe_50/2'>A2 stacks with Phe 50</scene> in β3. These aromatic side chains form hydrophobic interactions with the ligand when stacked (Figure 3). Also, the residue <scene name='78/781963/C1_a2_phe48/2'>F48 inserts between the sugar rings of C1 and A2</scene>. <scene name='78/781963/C1_binding_pocket3/1'>C1 is recognized definitively by the RRM</scene>. The amino proton of C1 hydrogen bonds with the carbonyl oxygen of Leu 80 and the side-chain carbonyl oxygen of Glu 79, the N3 of C1 hydrogen bonds with the amide of Asn 82, and the O2 of C1 hydrogen bonds with the hydroxyl group of Ser 81<ref name="Hargous">PMID:17036044</ref>.
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1H-15N HSQC results showed a large hydrophobic β-sheet on the RRM binding to the RNA with all four bases interacting with one of the four aromatic residues via hydrophobic interactions <ref name="Hargous">PMID:17036044</ref>. [https://en.wikipedia.org/wiki/Beta_hairpin β-hairpin] amino acids are hydrogen bonded to bases on nucleic acid targets <ref name="Clery">PMID:18515081</ref>. This suggests that the β-hairpin plays a role in SRp20 selectivity for specific ligands. The researchers used a smaller peptide chain to reduce the NMR broadening seen with longer peptides (allowing for structure determination), with the consequence of reduced binding affinity.
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The ligand used was <scene name='78/781963/Looking_at_the_ligand/1'>CAUC</scene>. The conformation of U3 and C4 shows that U3 bulges out while C4 partially stacks over A2. Interactions with the RRM that the researchers saw were that <scene name='78/781963/C1_and_tyr_13/3'>C1 stacks with Tyr 13</scene> in β1 and <scene name='78/781963/A2_phe_50/2'>A2 stacks with Phe 50</scene> in β3. These aromatic side chains form hydrophobic interactions with the ligand when stacked (Figure 3). Also, the residue <scene name='78/781963/C1_a2_phe48/2'>F48 inserts between the sugar rings of C1 and A2</scene>. <scene name='78/781963/C1_binding_pocket3/1'>C1 is recognized definitively by the RRM</scene>. The amino proton of C1 hydrogen bonds with the carbonyl oxygen of Leu 80 and the side-chain carbonyl oxygen of Glu 79. The N3 of C1 hydrogen bonds with the amide of Asn 82, and the O2 of C1 hydrogen bonds with the hydroxyl group of Ser 81<ref name="Hargous">PMID:17036044</ref>.
It was also noted that <scene name='78/781963/A2_syn_conformation/1'>A2</scene> adopts an unusual syn conformation. U3 interacts with <scene name='78/781963/U3_hydrophobic_interactions/2'>Phe 48, Trp 40, Ala 42,</scene> and with the β2-3 loop of the RRM. These residues are all hydrophobic, offering a large hydrophobic surface that helps bind the ligand, as well as prevents the solvent from binding. Additionally, C4 is maintained in its position by a <scene name='78/781963/C4_a2_h_bond/1'>hydrogen bond between C4 amino group and the A2 2’ oxygen</scene> <ref name="Hargous">PMID:17036044</ref>. [[Image:Figure_4_C1_and_A2_interactions_Edited2.png|300 px|left|thumb|Figure 3: C1 and A2 on the RNA ligand interacting with hydrophobic residues (Tyr 13, Phe 50, Phe 48) in the RRM domain of the SRp20 protein. Image created using ''Pymol'']]
It was also noted that <scene name='78/781963/A2_syn_conformation/1'>A2</scene> adopts an unusual syn conformation. U3 interacts with <scene name='78/781963/U3_hydrophobic_interactions/2'>Phe 48, Trp 40, Ala 42,</scene> and with the β2-3 loop of the RRM. These residues are all hydrophobic, offering a large hydrophobic surface that helps bind the ligand, as well as prevents the solvent from binding. Additionally, C4 is maintained in its position by a <scene name='78/781963/C4_a2_h_bond/1'>hydrogen bond between C4 amino group and the A2 2’ oxygen</scene> <ref name="Hargous">PMID:17036044</ref>. [[Image:Figure_4_C1_and_A2_interactions_Edited2.png|300 px|left|thumb|Figure 3: C1 and A2 on the RNA ligand interacting with hydrophobic residues (Tyr 13, Phe 50, Phe 48) in the RRM domain of the SRp20 protein. Image created using ''Pymol'']]

Revision as of 16:20, 10 April 2018

Biological Structure of SRp20

SRp20 Structure

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Alexis Neyman

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