Induced structural changes of 7SL RNA during the assembly of human signal recognition particle.
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.
Kuglstatter
Andreas
A
MRC Laboratory of Molecular Biology, Hills Road, Cambridge CB2 2QH, UK.
Oubridge
Chris
C
Nagai
Kiyoshi
K
D000595:Amino Acid Sequence; D001483:Base Sequence; D003001:Cloning, Molecular; D018360:Crystallography, X-Ray; D004926:Escherichia coli; D006801:Humans; D046911:Macromolecular Substances; D008969:Molecular Sequence Data; D011487:Protein Conformation; D020733:RNA, Small Cytoplasmic / Q000737:chemistry* / Q000378:metabolism; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins; D016415:Sequence Alignment; D018271:Signal Recognition Particle / Q000737:chemistry* / Q000378:metabolism
C115990:7SL RNA; D046911:Macromolecular Substances; D020733:RNA, Small Cytoplasmic; D011994:Recombinant Proteins; C117074:SRP19 protein, human; C069268:SRP54 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D018271:Signal Recognition Particle