During the co-translational translocation of secretory and integral membrane proteins into the endoplasmic reticulum (ER), the signal recognition particle (SRP) associates with a nascent chain-ribosome complex and targets it to the ER membrane by interacting with the SRP receptor (SR) which is localized in the ER membrane. This process is catalyzed by a cascade of three directly interacting GTPases: the 54kD subunit of SRP (SRP54), the alpha and beta subunits of SR (SRalpha and SRbeta). Both SRalpha and SRbeta are essential for SR function. While the functions of SRP54 and SRalpha have started to be elucidated, nothing is known about the role of SRbeta in the process. The experiments proposed here are designed to solve this mystery. Specifically, I will try to decipher the function of SRbeta by identifying and characterizing effector(s) and regulatory proteins that modulate its GTPase function. Such proteins are predicted to exist based on the common features of other well studied small GTPases that are shared with SRbeta. Specifically, I will ask whether the GTPase activities of SRbeta are regulated by SRalpha or vice Versa. Then, I will identify additional SRbeta interacting proteins and characterize them using a combination of biochemical and genetic approaches using the yeast Saccharomyces cerevisiae as the experimental system. Results derived from a functional characterization of the regulators and effector(s) of SRbeta will be used to develop hypotheses as to the function of its GTPase switch in protein translocation.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32GM019241-02
Application #
6017051
Study Section
Special Emphasis Panel (ZRG3-BIO (01))
Project Start
1999-06-01
Project End
Budget Start
1999-06-01
Budget End
2000-05-31
Support Year
2
Fiscal Year
1999
Total Cost
Indirect Cost
Name
University of California San Francisco
Department
Biochemistry
Type
Schools of Medicine
DUNS #
073133571
City
San Francisco
State
CA
Country
United States
Zip Code
94143