Model for signal sequence recognition from amino-acid sequence of 54K subunit of signal recognition particle.
Protein targeting to the endoplasmic reticulum in mammalian cells is catalysed by signal recognition particle (SRP). Cross-linking experiments have shown that the subunit of relative molecular mass 54,000 (Mr 54K; SRP54) interacts directly with signal sequences as they emerge from the ribosome. Here we present the sequence of a complementary DNA clone of SRP54 which predicts a protein that contains a putative GTP-binding domain and an unusually methionine-rich domain. The properties of this latter domain suggest that it contains the signal sequence binding site. A previously uncharacterized Escherichia coli protein has strong homology to both domains. Closely homologous GTP-binding domains are also found in the alpha-subunit of the SRP receptor (SR alpha, docking protein) in the endoplasmic reticulum membrane and in a second E. coli protein, ftsY, which resembles SR alpha. Recent work has shown that SR alpha is a GTP-binding protein and that GTP is required for the release of SRP from the signal sequence and the ribosome on targeting to the endoplasmic reticulum membrane. We propose that SRP54 and SR alpha use GTP in sequential steps of the targeting reaction and that essential features of such a pathway are conserved from bacteria to mammals.
Bernstein
H D
HD
Department of Biochemistry and Biophysics, University of California Medical School, San Francisco 94143-0448.
Poritz
M A
MA
Strub
K
K
Hoben
P J
PJ
Brenner
S
S
Walter
P
P
D000595:Amino Acid Sequence; D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics; D001483:Base Sequence; D003001:Cloning, Molecular; D004247:DNA / Q000235:genetics; D004285:Dogs; D004926:Escherichia coli / Q000235:genetics; D019204:GTP-Binding Proteins / Q000235:genetics; D046911:Macromolecular Substances; D051379:Mice; D008962:Models, Theoretical; D008969:Molecular Sequence Data; D008970:Molecular Weight; D010179:Pancreas / Q000378:metabolism; D021382:Protein Sorting Signals / Q000235:genetics*; D015183:Restriction Mapping; D012689:Sequence Homology, Nucleic Acid
D001426:Bacterial Proteins; D046911:Macromolecular Substances; D021382:Protein Sorting Signals; D004247:DNA; D019204:GTP-Binding Proteins