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Induced structural changes of 7SL RNA during the assembly of human signal recognition particle

Abstract

The eukaryotic signal recognition particle (SRP) is a cytoplasmic ribonucleoprotein particle that targets secretory and membrane proteins to the endoplasmic reticulum. The binding of SRP54 to the S domain of 7SL RNA is highly dependent on SRP19. Here we present the crystal structure of a human SRP ternary complex consisting of SRP19, the M domain of SRP54 and the S domain of 7SL RNA. Upon binding of the M domain of SRP54 to the 7SL RNA–SRP19 complex, the asymmetric loop of helix 8 in 7SL RNA collapses. The bases of the four nucleotides in the long strand of the asymmetric loop continuously stack and interact with the M domain, whereas the two adenines in the short strand flip out and form two A-minor motifs with helix 6. This stabilizing interaction is only possible when helix 6 has been positioned parallel to helix 8 by the prior binding of SRP19 to the tetraloops of helices 6 and 8. Hence, the crystal structure of the ternary complex suggests why SRP19 is necessary for the stable binding of SRP54 to the S domain RNA.

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Figure 1: Overview of the ternary complex between SRP19, the M domain of SRP54 and the S domain RNA.
Figure 2: Conformational changes of the S domain RNA upon binding of the M domain.
Figure 3: Interaction between the M domain and the RNA.
Figure 4: Changes in the structure of the S domain RNA during S domain assembly.

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Acknowledgements

G. Leonard and C. Jamin provided excellent support at the ESRF (Grenoble, France) beamlines ID14-4 and ID14-2. We thank A. Leung and E. Menichelli for their assistance in data collection and P.R. Evans, J. Li and L. Jovine for their help in structure determination. We thank V. Ramakrishnan for helpful discussion and A. Lenton for drawing figures. A.K has been supported by a post-graduate fellowship of the Boehringer Ingelheim Fonds.

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Correspondence to Kiyoshi Nagai.

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Kuglstatter, A., Oubridge, C. & Nagai, K. Induced structural changes of 7SL RNA during the assembly of human signal recognition particle. Nat Struct Mol Biol 9, 740–744 (2002). https://doi.org/10.1038/nsb843

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