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, SRalpha, and SRbeta, which act in concert. Little is known about the regulatory role of SRbeta. Here, we present the 1.7 Angstrom crystal structure of the SRbeta-GTP subunit in complex with the interaction domain of SRalpha. Strikingly, the binding interface overlaps largely with the switch 1 region of SRbeta. 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 SRbeta functions as a regulatory switch for the receptor dimerization. We discuss the implications for the translocation pathway.