Crystal structure of the conserved subdomain of human protein SRP54M at 2.1 A resolution: evidence for the mechanism of signal peptide binding
Protein SRP54 is an integral part of the mammalian signal recognition particle (SRP), a cytosolic ribonucleoprotein complex which associates with ribosomes and serves to recognize, bind, and transport proteins destined for the membrane or secretion. The methionine-rich M-domain of protein SRP54 (SRP54M) binds the SRP RNA and the signal peptide as the nascent protein emerges from the ribosome. A focal point of this critical cellular function is the detailed understanding of how different hydrophobic signal peptides are recognized efficiently and transported specifically, despite considerable variation in sequence. We have solved the crystal structure of a conserved functional subdomain of the human SRP54 protein (hSRP54m) at 2.1 Å resolution showing a predominantly alpha helical protein with a large fraction of the structure available for binding. RNA binding is predicted to occur in the vicinity of helices 4 to 6. The N-terminal helix extends significantly from the core of the structure into a large but constricted hydrophobic groove of an adjacent molecule, thus revealing molecular details of possible interactions between alpha helical signal peptides and human SRP54.
© 1999 Academic Press. Received 21 May 1999, Revised 29 July 1999, Accepted 29 July 1999, Available online 25 May 2002. We thank R.M. Sweet and S.J. Sclafani for help with data collection at NSLS. The diffraction facility at beamlines X12-C and X25 at the NSLS at Brookhaven is supported by the United States Department of Energy offices of Health and Environmental Research and of Basic Energy Sciences, and by the National Science Foundation. Supported by a NIH GMS grant to C.Z.