Structural Basis for the Function of the β Subunit of the Eukaryotic Signal Recognition Particle Receptor

Protein translocation across and insertion into membranes is a process essential to all life forms. In higher eukaryotes, this process is initiated by targeting the translating ribosome to the endoplasmic reticulum via the signal recognition particle (SRP) and its membrane-associated heterodimeric receptor (SR). This targeting step is regulated by three G proteins, SRP54, SRα, and SRβ, which act in concert. Little is known about the regulatory role of SRβ. Here, we present the 1.7 Å crystal structure of the SRβ-GTP subunit in complex with the interaction domain of SRα. Strikingly, the binding interface overlaps largely with the switch 1 region of SRβ. This finding, together with additional biochemical data, shows that the eukaryotic SR is a conditional and not an obligate heterodimer. The results suggest that the GTP/GDP switch cycle of SRβ functions as a regulatory switch for the receptor dimerization. We discuss the implications for the translocation pathway.