SRP/SRP receptor complex
Thermus aquaticus (bacteria)
Signal sequences and signal patches direct proteins to the correct cellular address, for example secretion from cells or integration into cell membranes. The endoplasmic reticulum (ER) signal sequence is guided to the ER membrane by at least two components, a signal recognition particle (SRP) and its receptor (SR). The SRP binds to both the exposed ER signal sequence and the ribosome, thereby inducing a pause in translation. The SR in the ER membrane, which is composed of two different polypeptide chains,binds the SRP-ribosome complex and directs in to the translocator. The SRP and SR are then released, leaving the ribosome bound to the translocator. The translocator then inserts the polypeptide chain into the membrane and transfers it across the lipid bilayer. The SRP and SR contain GTP-binding domain. In the complex of the SRP and SR, the SRP and SR stimulate each other's GTPase activity, and the conformational changes that occur during cycles of GTP binding and hydrolysis ensure that SRP release occurs only after the ribosome has become properly engaged with the translocator in the ER membrane.
The structure of the catalytic core formed by the Thermus aquaticus SRP receptor (FtsY) and the amino-terminal N and the GTPase G domains of the SRP protein (Ffh) in the presence of the non-hydrolysabale GTP analogue GMPPCP was determined at 1.9 angstrom resolution. The two partners form a quasi-twofold structure that aligns the two GTP molecules in a symmetrical, composite active site. The 3' OH groups are essential for association, reciprocal activation and catalysis. Each GTPase provides its own catalytic machinery when in cis conformation and is stimulated when in trans conformation by hydrogen bonds between the twinned GTPs. This unique circle of twinned interactions is severed twice on hydrolysis, leading to complex dissociation after cargo delivery.
Protein Data Bank (PDB)
Egea, P.F. Shan, S.O. Napetschnig, J. Savage, D.F. Walter, P. Stroud, R.M.; "Substrate twinning activates the signal recognition particle and its receptor"; Nature; (2004) 427:215-221 PubMed:14724630.
author: Naoyuki Miyazaki