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Crystal structure of the spliceosomal U2B″–U2A′ protein complex bound to a fragment of U2 small nuclear RNA

Nature volume 394, pages 645–650 (1998)Cite this article

Abstract

We have determined the crystal structure at 2.4 å resolution of a ternary complex between the spliceosomal U2B″/U2A′ protein complex and hairpin-loop IV of U2 small nuclear RNA. Unlike its close homologue the U1A protein, U2B″ binds to its cognate RNA only in the presence of U2A′, which contains leucine-rich repeats in its sequence. The concave surface of a parallel β-sheet within the leucine-rich-repeat region of U2A′ interacts with the ribonucleoprotein domain of U2B″ on the surface opposite its RNA-binding surface. The basic carboxy-terminal region of U2A′ interacts with the RNA stem. The crystal structure reveals how protein–protein interaction regulates RNA-binding specificity, and how replacing only a few key residues allows the U2B″ and U1A proteins to discriminate between their cognate RNA hairpins by forming alternative networks of interactions.

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Figure 1: Amino-acid sequences of the U2B″ and U2A′ (U2LRR) proteins and their RNA binding site.
Figure 2: Overall structure of the U2B″–U2A′ (U2LRR) protein complex bound to hairpin IV of U2 snRNA.
Figure 3: Comparison of the RNA–protein interfaces between the U2B″/U2LRR(U2A′)/RNA complex and the U1A protein–RNA complex10.
Figure 4: Interaction between U2A′ (U2 LRR) protein and the RNA stem in the U2B″/U2LRR/RNA and hypothetical U1A/U2LRR/RNA complexes.

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Acknowledgements

We thank W. Scott, E. de la Fortelle, J Li, H. Teo, C. Oubridge and C. Kambach, L.Jovine and A. McCoy for their help; M. Perutz, A. Klug, D. Rhodes and J. Schwabe for critically reading the manuscript; G. Lingley, A. Lenton and K. Nagai for the illustrations; and staff at the ELETTRA, Daresbury and EMBL Hamburg synchrotrons for help with data collection. S.R.P. was supported by an MRC studentship. This project was funded by the MRC and Human Frontier Science Program.

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  1. Stephen R. Price

    Present address: Department of Biochemistry and Molecular Biophysics, Columbia University, 701 West 168th Street, New York, New York, 10032, USA

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  1. MRC Laboratory of Molecular Biology, Hills Road, CB2 2QH, Cambridge, UK

    Philip R. Evans & Kiyoshi Nagai

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Price, S., Evans, P. & Nagai, K. Crystal structure of the spliceosomal U2B″–U2A′ protein complex bound to a fragment of U2 small nuclear RNA. Nature 394, 645–650 (1998). https://doi.org/10.1038/29234

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