Question

What is the GTPAses for the pathway of cytoplasm to the rough endoplasmic?

Answer 1

Cotranslational translocation occurs when membrane-bound ribosomes insert growing nascent polypeptide chains directly into an ER translocation pore. The targeting of cytoplasmic ribosomes translating signal sequence-containing polypeptides to the ER is mediated by the signal recognition particle (SRP). SRP is a cytoplasmic, ribonucleoprotein particle comprised of 6 proteins . Recent structural studies on SRP constituents suggest that the highly conserved RNA in this particle mediates SRP assembly and signal sequence recognition. SRP binds to a signal sequence emerging from the ribosome and slows protein synthesis, which is thought to allow time for a ribosome-nascent chain complex to diffuse to the ER membrane. If translation were not slowed, the premature folding of a secreted protein in the cytoplasm would preclude its translocation. Upon arriving at the ER membrane SRP interacts with the SRP receptor (SR), SRP is released, and translation resumes. The docking and release of SRP at the ER membrane requires GTP. Overall, this cycle guarantees that translation is tightly coupled to translocation.

The answer lies in part through the observation that both SRP and SR are GTPases. SR54, the ?54 kDa component of SRP, and SR? a soluble constituent of SR, both belong to a structurally unique family of GTPases. GTP binding by SRP54 and SR? is required for the SR-dependent release of the signal sequence from SRP and GTP hydrolysis by SRP54 and SR? must precede the subsequent dissociation of SRP from SR. Still controversial, however, is whether SRP interacts initially with ribosome-nascent chain complexes: (A) in a nucleotide-free state, which would require nucleotide binding and hydrolysis at the ER membrane upon SR interaction, (B) in the GDP state, which would require that the ribosome triggers nucleotide exchange prior to association with the SR, or (C) in the GTP-bound state, which would require that GTP hydrolysis is inhibited until SR docking occurs. This picture is complicated further by the fact that SR? is tethered to the ER membrane by the integral membrane SR? subunit, which is also a GTPase; the nucleotide-bound state of SR? controls whether SR? is free or attached to the ER membrane and it has been suggested that a component of the translocation pore regulates nucleotide exchange on SR?.Regardless, the targeting of ribosome-nascent chain complexes to the ER translocation machinery and the subsequent recycling of SRP are intimately regulated by the GTPase cycle of SRP54 and SR?/?.