Structural basis for the function of the beta 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, SR alpha, and SR beta, which act in concert. Little is known about the regulatory role of SR beta. Here, we present the 1.7 A crystal structure of the SR beta-GTP subunit in complex with the interaction domain of SR alpha. Strikingly, the binding interface overlaps largely with the switch 1 region of SR beta. 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 SR beta functions as a regulatory switch for the receptor dimerization. We discuss the implications for the translocation pathway.
Schwartz
Thomas
T
Howard Hughes Medical Institute, Laboratory of Cell Biology, The Rockefeller University, 1230 York Avenue, New York, NY 10021, USA.
Blobel
Günter
G
D000595:Amino Acid Sequence; D017124:Conserved Sequence; D018360:Crystallography, X-Ray; D019281:Dimerization; D004721:Endoplasmic Reticulum / Q000378:metabolism; D005057:Eukaryotic Cells; D019204:GTP-Binding Proteins / Q000737:chemistry / Q000378:metabolism; D006160:Guanosine Triphosphate / Q000378:metabolism; D008958:Models, Molecular; D015394:Molecular Structure; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D021122:Protein Subunits / Q000737:chemistry* / Q000378:metabolism; D021381:Protein Transport; D018160:Receptors, Cytoplasmic and Nuclear / Q000737:chemistry* / Q000378:metabolism; D018000:Receptors, Peptide / Q000737:chemistry* / Q000378:metabolism; D012270:Ribosomes / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D018271:Signal Recognition Particle / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D013329:Structure-Activity Relationship
D021122:Protein Subunits; D018160:Receptors, Cytoplasmic and Nuclear; D018000:Receptors, Peptide; D029701:Saccharomyces cerevisiae Proteins; D018271:Signal Recognition Particle; C036318:signal peptide receptor; D006160:Guanosine Triphosphate; D019204:GTP-Binding Proteins