Structure of the complete bacterial SRP Alu domain.
Bottom Line: The mammalian Alu domain is a protein-RNA complex, while prokaryotic Alu domains are protein-free with significant extensions of the RNA.The 5' region includes an extended loop-loop pseudoknot made of five consecutive Watson-Crick base pairs.Homology modeling with the human Alu domain in context of the ribosome shows that an additional lobe in the pseudoknot approaches the large subunit, while the absence of protein results in the detachment from the small subunit.
Affiliation: Heidelberg University Biochemistry Center (BZH), INF 328, D-69120 Heidelberg, Germany.Show MeSH
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Mentions: The signal recognition particle (SRP) plays an essential role in co-translational targeting of newly synthesized membrane proteins (1,2). SRP is a ribonucleoprotein complex conserved in all three kingdoms of life with a high diversity regarding composition and complexity (3). Eukaryotic SRP contains six proteins assembled on a 7SL RNA (4) and can be divided into two functional domains. While the S domain recognizes SRP targets through their N-terminal signal sequences as soon as they emerge from the ribosomal tunnel exit, the Alu domain imposes an elongation arrest by blocking the elongation factor entry site (5–8). By retarding translation, SRP prevents membrane proteins from being prematurely released from the ribosome before the ribosome-nascent chain complex (RNC) has correctly engaged with the translocation channel at the endoplasmic reticulum membrane (1,9). The Alu domain of higher eukaryotes is composed of the 5′ and 3′ regions of SRP RNA and the two Alu RNA-specific proteins SRP9/14 (Figure 1A). The proteins stabilize the complex tertiary structure of the Alu RNA and contribute to ribosome binding (10–12). In a cryo-EM structure of mammalian SRP bound to the RNC, the SRP9/14 proteins were shown to interact with the small ribosomal subunit, while the Alu RNA establishes a contact with the large ribosomal subunit (12,13). The structure of the Alu RNA is instructive also for understanding of the retrotransposable, repetitive Alu elements, which comprise more than 10% of the primate genome and are derived from the 7SL RNA (14–18). Despite their abundance, the precise roles of Alu elements are still poorly understood, and their function in gene regulation or as templates for the production of new exons is just emerging (18,19).
Affiliation: Heidelberg University Biochemistry Center (BZH), INF 328, D-69120 Heidelberg, Germany.