The beta subunit of the signal recognition particle receptor is a transmembrane GTPase that anchors the alpha subunit, a peripheral membrane GTPase, to the endoplasmic reticulum membrane

doi:10.1083/jcb.128.3.273

This Article

	Full Text (PDF, 1770K)
	Alert me when this article is cited
	Citation Map

Services

	Email this article
	Similar articles in this journal
	Similar articles in PubMed
	Alert me to new content in the JCB
	Download to citation manager

Citing Articles

	Citing Articles via HighWire
	Citing Articles via CrossRef
	Citing Articles via Google Scholar

Google Scholar

	Articles by Miller, J. D.
	Articles by Walter, P.
	Search for Related Content

PubMed

	PubMed Citation
	Articles by Miller, J. D.
	Articles by Walter, P.


Social Bookmarking

	What's this?

ARTICLES

The beta subunit of the signal recognition particle receptor is a transmembrane GTPase that anchors the alpha subunit, a peripheral membrane GTPase, to the endoplasmic reticulum membrane

JD Miller, S Tajima, L Lauffer and P Walter
Department of Biochemistry and Biophysics, University of California Medical School, San Francisco 94143-0448.

The signal recognition particle receptor (SR) is required for the cotranslational targeting of both secretory and membrane proteins to the endoplasmic reticulum (ER) membrane. During targeting, the SR interacts with the signal recognition particle (SRP) which is bound to the signal sequence of the nascent protein chain. This interaction catalyzes the GTP-dependent transfer of the nascent chain from SRP to the protein translocation apparatus in the ER membrane. The SR is a heterodimeric protein comprised of a 69-kD subunit (SR alpha) and a 30- kD subunit (SR beta) which are associated with the ER membrane in an unknown manner. SR alpha and the 54-kD subunits of SRP (SRP54) each contain related GTPase domains which are required for SR and SRP function. Molecular cloning and sequencing of a cDNA encoding SR beta revealed that SR beta is a transmembrane protein and, like SR alpha and SRP54, is a member of the GTPase superfamily. Although SR beta defines its own GTPase subfamily, it is distantly related to ARF and Sar1. Using UV cross-linking, we confirm that SR beta binds GTP specifically. Proteolytic digestion experiments show that SR alpha is required for the interaction of SRP with SR. SR alpha appears to be peripherally associated with the ER membrane, and we suggest that SR beta, as an integral membrane protein, mediates the membrane association of SR alpha. The discovery of its guanine nucleotide-binding domain, however, makes it likely that its role is more complex than that of a passive anchor for SR alpha. These findings suggest that a cascade of three directly interacting GTPases functions during protein targeting to the ER membrane.
Add to CiteULike CiteULike Add to Complore Complore Add to Connotea Connotea Add to Del.icio.us Del.icio.us Add to Digg Digg Add to Reddit Reddit Add to Technorati Technorati What's this?

This article has been cited by other articles:

Schwartz, T. U., Schmidt, D., Brohawn, S. G., Blobel, G. (2006). Homodimerization of the G protein SRbeta in the nucleotide-free state involves proline cis/trans isomerization in the switch II region. Proc. Natl. Acad. Sci. USA 103: 6823-6828 [Abstract] [Full Text]
Schlenker, O., Hendricks, A., Sinning, I., Wild, K. (2006). The Structure of the Mammalian Signal Recognition Particle (SRP) Receptor as Prototype for the Interaction of Small GTPases with Longin Domains. J. Biol. Chem. 281: 8898-8906 [Abstract] [Full Text]
Griparic, L., van der Wel, N. N., Orozco, I. J., Peters, P. J., van der Bliek, A. M. (2004). Loss of the Intermembrane Space Protein Mgm1/OPA1 Induces Swelling and Localized Constrictions along the Lengths of Mitochondria. J. Biol. Chem. 279: 18792-18798 [Abstract] [Full Text]
Legate, K. R., Andrews, D. W. (2003). The {beta}-Subunit of the Signal Recognition Particle Receptor Is a Novel GTP-binding Protein without Intrinsic GTPase Activity. J. Biol. Chem. 278: 27712-27720 [Abstract] [Full Text]
Helmers, J., Schmidt, D., Glavy, J. S., Blobel, G., Schwartz, T. (2003). The {beta}-Subunit of the Protein-conducting Channel of the Endoplasmic Reticulum Functions as the Guanine Nucleotide Exchange Factor for the {beta}-Subunit of the Signal Recognition Particle Receptor. J. Biol. Chem. 278: 23686-23690 [Abstract] [Full Text]
Meacock, S. L., Lecomte, F. J.L., Crawshaw, S. G., High, S. (2002). Different Transmembrane Domains Associate with Distinct Endoplasmic Reticulum Components during Membrane Integration of a Polytopic Protein. Mol. Biol. Cell 13: 4114-4129 [Abstract] [Full Text]
Pool, M. R., Stumm, J., Fulga, T. A., Sinning, I., Dobberstein, B. (2002). Distinct Modes of Signal Recognition Particle Interaction with the Ribosome. Science 297: 1345-1348 [Abstract] [Full Text]
Gewurz, B. E., Ploegh, H. L., Tortorella, D. (2002). US2, a Human Cytomegalovirus-encoded Type I Membrane Protein, Contains a Non-cleavable Amino-terminal Signal Peptide. J. Biol. Chem. 277: 11306-11313 [Abstract] [Full Text]
Chung, J.-G., Yeh, K.-T., Wu, S.-L., Hsu, N.-Y., Chen, G.-W., Yeh, Y.-W., Ho, H.-C. (2001). Novel Transmembrane GTPase of Non-Small Cell Lung Cancer Identified by mRNA Differential Display. Cancer Res. 61: 8873-8879 [Abstract] [Full Text]
Batey, R. T., Rambo, R. P., Lucast, L., Rha, B., Doudna, J. A. (2000). Crystal Structure of the Ribonucleoprotein Core of the Signal Recognition Particle. Science 287: 1232-1239 [Abstract] [Full Text]
Tu, C.-J., Schuenemann, D., Hoffman, N. E. (1999). Chloroplast FtsY, Chloroplast Signal Recognition Particle, and GTP Are Required to Reconstitute the Soluble Phase of Light-harvesting Chlorophyll Protein Transport into Thylakoid Membranes. J. Biol. Chem. 274: 27219-27224 [Abstract] [Full Text]
Bacher, G., Pool, M., Dobberstein, B. (1999). The Ribosome Regulates the GTPase of the {beta}-subunit of the Signal Recognition Particle Receptor. JCB 146: 723-730 [Abstract] [Full Text]
Ogg, S. C., Barz, W. P., Walter, P. (1998). A Functional GTPase Domain, but not its Transmembrane Domain, is Required for Function of the SRP Receptor beta -subunit. JCB 142: 341-354 [Abstract] [Full Text]
Zelazny, A., Seluanov, A., Cooper, A., Bibi, E. (1997). The NG domain of the prokaryotic signal recognition particle receptor, FtsY, is fully functional when fused to an unrelated integral membrane�polypeptide. Proc. Natl. Acad. Sci. USA 94: 6025-6029 [Abstract] [Full Text]
Corsi, A. K., Schekman, R. (1996). Mechanism of Polypeptide Translocation into the Endoplasmic Reticulum. J. Biol. Chem. 271: 30299-30302 [Full Text]
Mallet, W., Brodsky, F. (1996). A membrane-associated protein complex with selective binding to the clathrin coat adaptor AP1. J. Cell Sci. 109: 3059-3068 [Abstract]
Bovia, F, Strub, K (1996). The signal recognition particle and related small cytoplasmic ribonucleoprotein particles. J. Cell Sci. 109: 2601-2608 [Abstract]
Powers, T, Walter, P (1995). Reciprocal stimulation of GTP hydrolysis by two directly interacting GTPases. Science 269: 1422-1424 [Abstract]
Justice, J. M., Murtagh, J. J. , Jr., Moss, J., Vaughan, M. (1995). Hydrophobicity and Subunit Interactions of Rod Outer Segment Proteins Investigated Using Triton X-114 Phase Partitioning. J. Biol. Chem. 270: 17970-17976 [Abstract] [Full Text]
Young, J. C., Ursini, J., Legate, K. R., Miller, J. D., Walter, P., Andrews, D. W. (1995). An Amino-terminal Domain Containing Hydrophobic and Hydrophilic Sequences Binds the Signal Recognition Particle Receptor [IMAGE] Subunit to the [IMAGE] Subunit on the Endoplasmic Reticulum Membrane. J. Biol. Chem. 270: 15650-15657 [Abstract] [Full Text]
Brown, J.D., Ng, D.T.W., Ogg, S.C., Walter, P. (1995). Targeting Pathways to the Endoplasmic Reticulum Membrane. Cold Spring Harb Symp Quant Biol 60: 23-30 [Abstract]
Pagani, M., Fabbri, M., Benedetti, C., Fassio, A., Pilati, S., Bulleid, N. J., Cabibbo, A., Sitia, R. (2000). Endoplasmic Reticulum Oxidoreductin 1-Lbeta (ERO1-Lbeta ), a Human Gene Induced in the Course of the Unfolded Protein Response. J. Biol. Chem. 275: 23685-23692 [Abstract] [Full Text]
Legate, K. R., Falcone, D., Andrews, D. W. (2000). Nucleotide-dependent Binding of the GTPase Domain of the Signal Recognition Particle Receptor beta -Subunit to the alpha -Subunit. J. Biol. Chem. 275: 27439-27446 [Abstract] [Full Text]