Model for signal sequence recognition from amino-acid sequence of 54K subunit of signal recognition particle

Abstract

PROTEIN targeting to the endoplasmic reticulum in mammalian cells is catalysed by signal recognition particle (SRP)^1,2. Cross-linking experiments have shown that the subunit of relative molecular mass 54,000 (M_r 54K; SRP54) interacts directly with signal sequences as they emerge from the ribosome^3,4. 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 α-subunit of the SRP receptor (SRα, docking protein) in the endoplasmic reticulum membrane^5-8 and in a second E. coli protein, ftsY, which resembles SRα. Recent work has shown that SRα 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 membrane⁹. We propose that SRP54 and SRα use GTP in sequential steps of the targeting reaction and that essential features of such a pathway are conserved from bacteria to mammals.