User:David Ryskamp/Sandbox1: Difference between revisions

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== Background ==
== Background ==
The Human Poly(A) Binding Protein [https://www.rcsb.org/structure/1cvj (PABP)] was discovered in 1973 by the use of a sedimentation profile detailing the RNase digestion differentiated the PABP protein. <ref name="A Protein of Molecular Weight 78,000">Blobel, Gunter. “A Protein of Molecular Weight 78,000 Bound to the Polyadenylate Region of Eukaryotic Messenger Rnas.” Proceedings of the National Academy of Sciences of the United States of America, vol. 70, no. 3, 1973, pp. 924–8.</ref> Attempts to purify the 75 kDa protein then followed. In 1983, then considered “poly(A)-organizing protein,” was determined and purified by molecular weight, ligand-binding affinity, and amounts found in cytoplasmic portions of cell with ability to bind to free poly(A). <ref name="Cytoplasmic Poly(A)">Baer, Bradford W. and Kornberg, Roger D. "The Protein Responsible for the Repeating Structure of Cytoplasmic Poly(A)-Ribonucleoprotein." The Journal of Cell Biology, vol. 96, no. 3, Mar. 1983, pp. 717-721. EBSCOhost. </ref> The protein’s structure was initially determined at 2.6 Å as mRNA and RRM 1 & 2 yielded high cocrystal quality with 1:1 protein and ligand.<ref name="Recognition of Polyadenylate RNA by the Poly(A)-Binding Protein">Deo, Rahul C, et al. “Recognition of Polyadenylate RNA by the Poly(A)-Binding Protein.” Cell 98:6. (1999) 835-845. Print. </ref>  The protein has a homopolymeric structure, containing four RNA recognition motifs (RRMs), which are conserved. <ref name="Structure and Function">Kühn, Uwe and Elmar, Wahle. “Structure and Function of Poly(a) Binding Proteins.” Bba - Gene Structure & Expression, vol. 1678, no. 2/3, 2004. </ref> <scene name='78/782616/Rrm1_only/2'>RRM1</scene> and <scene name='78/782616/Rrm2_only/2'>RRM2</scene> are N-terminal domains that are connected by a <scene name='78/782616/Linker/3'>linker</scene>.<ref name="Recognition of Polyadenylate RNA by the Poly(A)-Binding Protein">Deo, Rahul C, et al. “Recognition of Polyadenylate RNA by the Poly(A)-Binding Protein.” Cell 98:6. (1999) 835-845. Print. </ref> Opposed to their counterparts, RRM3 and RRM4 bind Poly (A) RNA less tightly than RRM1 and RRM2.<ref name="Recognition of Polyadenylate RNA by the Poly(A)-Binding Protein">Deo, Rahul C, et al. “Recognition of Polyadenylate RNA by the Poly(A)-Binding Protein.” Cell 98:6. (1999) 835-845. Print. </ref>
The Human Poly(A) Binding Protein [https://www.rcsb.org/structure/1cvj (PABP)] was discovered in 1973 by the use of a sedimentation profile detailing the RNase digestion differentiated the PABP protein. <ref name="A Protein of Molecular Weight 78,000">Blobel, Gunter. “A Protein of Molecular Weight 78,000 Bound to the Polyadenylate Region of Eukaryotic Messenger Rnas.” Proceedings of the National Academy of Sciences of the United States of America, vol. 70, no. 3, 1973, pp. 924–8.</ref> Attempts to purify the 75 kDa protein then followed. In 1983, then considered “poly(A)-organizing protein,” was determined and purified by molecular weight, ligand-binding affinity, and amounts found in cytoplasmic portions of cell with ability to bind to free poly(A). <ref name="Cytoplasmic Poly(A)">Baer, Bradford W. and Kornberg, Roger D. "The Protein Responsible for the Repeating Structure of Cytoplasmic Poly(A)-Ribonucleoprotein." The Journal of Cell Biology, vol. 96, no. 3, Mar. 1983, pp. 717-721. EBSCOhost. </ref>  
   
   


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== Structure ==
== Structure ==


The crystal structure PABP was derived from X-ray Diffraction at 2.6Å (R-value: 23%). The subunits of PABP, RRM1 and RRM2, are examined in this article as the ''in vivo'' form seen in biological assembly 1 (via PDB).  
The crystal structure PABP was derived from X-ray Diffraction at 2.6Å (R-value: 23%). The subunits of PABP, RRM1 and RRM2, are examined in this article as the ''in vivo'' form seen in biological assembly 1 (via PDB). The protein has a homopolymeric structure, containing four RNA recognition motifs (RRMs), which are conserved. <ref name="Structure and Function">Kühn, Uwe and Elmar, Wahle. “Structure and Function of Poly(a) Binding Proteins.” Bba - Gene Structure & Expression, vol. 1678, no. 2/3, 2004. </ref> <scene name='78/782616/Rrm1_only/2'>RRM1</scene> and <scene name='78/782616/Rrm2_only/2'>RRM2</scene> are N-terminal domains that are connected by a <scene name='78/782616/Linker/3'>linker</scene>.<ref name="Recognition of Polyadenylate RNA by the Poly(A)-Binding Protein">Deo, Rahul C, et al. “Recognition of Polyadenylate RNA by the Poly(A)-Binding Protein.” Cell 98:6. (1999) 835-845. Print. </ref> Opposed to their counterparts, RRM3 and RRM4 bind Poly (A) RNA less tightly than RRM1 and RRM2.<ref name="Recognition of Polyadenylate RNA by the Poly(A)-Binding Protein">Deo, Rahul C, et al. “Recognition of Polyadenylate RNA by the Poly(A)-Binding Protein.” Cell 98:6. (1999) 835-845. Print. </ref>


===RNA Recognition Motifs (RRMs)===
===RNA Recognition Motifs (RRMs)===
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==Interactions==  
==Interactions==  


===Adenosine Recognition Interactions                                                                         mRNA Stabilization via Aromatic Stacking===                  
===Adenosine Recognition Interactions===                
<table><tr><td colspan='2'>  
<table><tr><td colspan='2'>  
<tr id='Nucleotide'><td class="sblockLbl"><b>Nucleotide</b></td><td class="sblockDat">PABP residue</td><td class="sblockDat">Atom on PABP residue</td>
<tr id='Nucleotide'><td class="sblockLbl"><b>Nucleotide</b></td><td class="sblockDat">PABP residue</td><td class="sblockDat">Atom on PABP residue</td>