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Crystallographic analysis of polypyrimidine tract-binding protein-Raver1 interactions involved in regulation of alternative splicing.

Joshi A, Coelho MB, Kotik-Kogan O, Simpson PJ, Matthews SJ, Smith CW, Curry S - Structure (2011)

Bottom Line: The polypyrimidine tract-binding protein (PTB) is an important regulator of alternative splicing.Our results refine the sequence of the PRI motif and place important structural constraints on functional models of PTB-Raver1 interactions.Our analysis indicates that the observed Raver1-PTB interaction is a general mode of binding that applies to Raver1 complexes with PTB paralogues such as nPTB and to complexes of Raver2 with PTB.

View Article: PubMed Central - PubMed

Affiliation: Division of Cell and Molecular Biology, Imperial College, Exhibition Road, London SW7 2AZ, UK.

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Detailed Structural Comparison of Raver1 PRI3 and PRI4 Bound to PTB RRM2(A and B) Close-up views of PRI3 bound to RRM2. Intramolecular hydrogen bonds are shown as orange dashes; intermolecular hydrogen bonds are yellow.(C and D) Equivalent views of PRI4 bound to RRM2.
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fig2: Detailed Structural Comparison of Raver1 PRI3 and PRI4 Bound to PTB RRM2(A and B) Close-up views of PRI3 bound to RRM2. Intramolecular hydrogen bonds are shown as orange dashes; intermolecular hydrogen bonds are yellow.(C and D) Equivalent views of PRI4 bound to RRM2.

Mentions: There is an extensive bipartite hydrophobic interface between the peptides and RRM2: the pair of Leu side chains at positions 2 and 3 in the motif both project into a shallow apolar depression between the two helices on the dorsal face of RRM2, whereas downstream residues of the PRIs are packed around the side chains of Tyr 247 and Tyr 193, though in very different conformations for the two peptides (Figure 2). For PRI3, the four-residue sequence 3LGAP6 wraps around Tyr 247 (Figure 2B), whereas in PRI4 a different backbone conformation means that just three residues, 3LGL5, are in contact with the tyrosine (Figure 2D). Moreover, although in PRI3 Pro 6 and Pro 7 both contact the side chains of Tyr 247 and Tyr 193, the equivalent residues in PRI4 (Gly 6 and Pro 7) are not visible in the electron density map, presumably due to disorder; this difference is likely to contribute to the lower affinity of PRI4. The occlusion of hydrophobic features on the surface of RRM2 by the Raver1 peptide probably accounts for the enhanced solubility of the chimeric PRI-RRM2 proteins.


Crystallographic analysis of polypyrimidine tract-binding protein-Raver1 interactions involved in regulation of alternative splicing.

Joshi A, Coelho MB, Kotik-Kogan O, Simpson PJ, Matthews SJ, Smith CW, Curry S - Structure (2011)

Detailed Structural Comparison of Raver1 PRI3 and PRI4 Bound to PTB RRM2(A and B) Close-up views of PRI3 bound to RRM2. Intramolecular hydrogen bonds are shown as orange dashes; intermolecular hydrogen bonds are yellow.(C and D) Equivalent views of PRI4 bound to RRM2.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3420021&req=5

fig2: Detailed Structural Comparison of Raver1 PRI3 and PRI4 Bound to PTB RRM2(A and B) Close-up views of PRI3 bound to RRM2. Intramolecular hydrogen bonds are shown as orange dashes; intermolecular hydrogen bonds are yellow.(C and D) Equivalent views of PRI4 bound to RRM2.
Mentions: There is an extensive bipartite hydrophobic interface between the peptides and RRM2: the pair of Leu side chains at positions 2 and 3 in the motif both project into a shallow apolar depression between the two helices on the dorsal face of RRM2, whereas downstream residues of the PRIs are packed around the side chains of Tyr 247 and Tyr 193, though in very different conformations for the two peptides (Figure 2). For PRI3, the four-residue sequence 3LGAP6 wraps around Tyr 247 (Figure 2B), whereas in PRI4 a different backbone conformation means that just three residues, 3LGL5, are in contact with the tyrosine (Figure 2D). Moreover, although in PRI3 Pro 6 and Pro 7 both contact the side chains of Tyr 247 and Tyr 193, the equivalent residues in PRI4 (Gly 6 and Pro 7) are not visible in the electron density map, presumably due to disorder; this difference is likely to contribute to the lower affinity of PRI4. The occlusion of hydrophobic features on the surface of RRM2 by the Raver1 peptide probably accounts for the enhanced solubility of the chimeric PRI-RRM2 proteins.

Bottom Line: The polypyrimidine tract-binding protein (PTB) is an important regulator of alternative splicing.Our results refine the sequence of the PRI motif and place important structural constraints on functional models of PTB-Raver1 interactions.Our analysis indicates that the observed Raver1-PTB interaction is a general mode of binding that applies to Raver1 complexes with PTB paralogues such as nPTB and to complexes of Raver2 with PTB.

View Article: PubMed Central - PubMed

Affiliation: Division of Cell and Molecular Biology, Imperial College, Exhibition Road, London SW7 2AZ, UK.

Show MeSH
Related in: MedlinePlus