Empty site forms of the SRP54 and SR alpha GTPases mediate targeting of ribosome-nascent chain complexes to the endoplasmic reticulum.
The SRP54 and SR alpha subunits of the signal recognition particle (SRP) and the SRP receptor (SR) undergo a tightly coupled GTPase cycle that mediates the signal sequence-dependent attachment of ribosomes to the Sec61 complex. Here, we show that SRP54 and SR alpha are in the empty site conformation prior to contact between the SRP-ribosome complex and the membrane-bound SR. Cooperative binding of GTP to SRP54 and SR alpha stabilizes the SRP-SR complex and initiates signal sequence transfer from SRP54 to Sec61 alpha. The GTP-bound conformations of SR alpha and SRP54 perform distinct roles, with SR alpha performing a predominant role in complex stabilization. Hydrolysis by both SRP54 and SR alpha is a prerequisite for dissociation of the SRP-SR complex.
Rapiejko
P J
PJ
Department of Biochemistry and Molecular Biology, University of Massachusetts Medical School, Worcester 01655-0103, USA.
Gilmore
R
R
D000818:Animals; D001483:Base Sequence; D001692:Biological Transport; D004285:Dogs; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D020558:GTP Phosphohydrolases / Q000378:metabolism*; D008861:Microsomes / Q000378:metabolism*; D008969:Molecular Sequence Data; D010194:Pancreatin; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D018000:Receptors, Peptide / Q000378:metabolism*; D012270:Ribosomes / Q000378:metabolism*; D018271:Signal Recognition Particle / Q000378:metabolism*
D018160:Receptors, Cytoplasmic and Nuclear; D018000:Receptors, Peptide; D018271:Signal Recognition Particle; C036318:signal peptide receptor; D010194:Pancreatin; D020558:GTP Phosphohydrolases