W0444

Structure of the Eukaryotic SRP-Receptor: New Insight into the Complex Regulation of Protein Targeting. Thomas Schwartz, Laboratory of Cell Biology, The Rockefeller Univ., 1230 York Ave., New York, NY 10021 USA.

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. The 1.7 Å crystal structure of the SRβ-GTP subunit in complex with the interaction domain of SRα was solved. Strikingly, the binding interface overlaps largely with the switch I region of SRβ. This finding, together with additional biochemical data, shows that the eukaryotic SR is a conditional and not an obligate heterodimer. SRβ functions as a regulatory switch for the dimerization of the receptor. This finding has new implications for the translocation pathway.