Structure and RNA Interactions of the N-Terminal RRM Domains of PTB

The polypyrimidine tract binding protein (PTB) is an important regulator of alternative splicing that also affects mRNA localization, stabilization, polyadenylation, and translation. NMR structural analysis of the N-terminal half of PTB (residues 55–301) shows a canonical structure for RRM1 but reve...

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Bibliographic Details
Published in:Structure (London) 2004-09, Vol.12 (9), p.1631-1643
Main Authors: Simpson, Peter J., Monie, Tom P., Szendröi, Andrea, Davydova, Natalia, Tyzack, Jonathan K., Conte, Maria R., Read, Christopher M., Cary, Peter D., Svergun, Dmitri I., Konarev, Peter V., Curry, Stephen, Matthews, Stephen
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Dimerization
Humans
Models, Molecular
Molecular Weight
Nuclear Magnetic Resonance, Biomolecular
Polypyrimidine Tract-Binding Protein - chemistry
Polypyrimidine Tract-Binding Protein - metabolism
Protein Binding
Protein Structure, Secondary
Protein Structure, Tertiary
RNA - metabolism
Sequence Alignment
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Summary:The polypyrimidine tract binding protein (PTB) is an important regulator of alternative splicing that also affects mRNA localization, stabilization, polyadenylation, and translation. NMR structural analysis of the N-terminal half of PTB (residues 55–301) shows a canonical structure for RRM1 but reveals novel extensions to the β strands and C terminus of RRM2 that significantly modify the β sheet RNA binding surface. Although PTB contains four RNA recognition motifs (RRMs), it is widely held that only RRMs 3 and 4 are involved in RNA binding and that RRM2 mediates homodimerization. However, we show here not only that the RRMs 1 and 2 contribute substantially to RNA binding but also that full-length PTB is monomeric, with an elongated structure determined by X-ray solution scattering that is consistent with a linear arrangement of the constituent RRMs. These new insights into the structure and RNA binding properties of PTB suggest revised models of its mechanism of action.
ISSN:0969-2126
1878-4186
DOI:10.1016/j.str.2004.07.008