Translocon

The signal recognition particle (SRP) is a cytosolic ribonucleoprotein complex which binds to signal sequences of nascent membrane and secretory proteins emerging from ribosomes. The SRP consists of a 7S RNA and at least six polypeptide subunits (relative molecular masses 9, 14, 19, 54, 68, and 72 kD). It induces an elongation arrest until the nascent chain/ ribosome/SRP complex reaches the translocon at the endoplasmic reticulum (ER) membrane. 

Multifunctional protein complex in the ER membrane. It translocates secretoiy proteins across and integrates membrane proteins into the ER membrane. The proteinconducting channel protein Sec61p is the most important component of the translocon. 

Transgenic Animal Models Transient Receptor Potential Transition State Translation Inhibitors Translocon... 

Potter, M. D., and Nicchitta, C. V. (2002). Endoplasmic reticulum-bound ribosomes reside in stable association with the translocon following termination of protein synthesis. J. Biol. Chem. 277, 23314-23320. 

Ribosomes (79-87) are small organelles 17-23 nm in diameter. They can exist in clusters known as polysomes or be attached to the er where they bind to pores in the er membrane. A major constituent of the er pore is translocon, the heterotrimetric Sec 61 protein complex. Sec 61 binds to the 80s ribosomes (86). Ribosomes consist of subunits, a 30s subunit (16srRNA and 21 proteins), and a 50s subunit (23s and 5s RNAs, > proteins and the catalytic site of peptidyl transferase). Ribosomes are the sites of protein synthesis. 

Fig. 3. Classification of single-spanning membrane proteins based on topology, (a) The loop model for explaining the biogenesis of type I topology in the translocon. The stop-transfer signal stops the integration, (b) Type I protein and a cleaved signal peptide, (c) Type II (NcytCexo) is made by a type II signal-anchor, (d) Type III (Nexo-Ccyto often called type I) is made by a type I signal-anchor, (e) Type IV (C-tail) is made independently from the translocon.

As described in Section II,C,2, some differences exist between the bacterial and eukaryotic systems on the multispanning membrane assembly (Gafvelin et al., 1997) however, they also have many points in common the multispanning membrane proteins are likely to be co-translationally integrated (Ulbrandt et al., 1997), and both systems use homologous translocon channels, which play an important role for the topogenesis of these multispanning membrane proteins (Prinz et al., 1998). 

Bibi, E. (1998). The role of the ribosome-translocon complex in translation and assembly of polytopic membrane proteins. Trends Biochem. Sci. 23, 51—55. 

Hamman, B., Hendershot, L., and Johnson, A. (1998). BiP maintains the permeability barrier of the ER membrane by sealing the lumenal end of the translocon pore before and early in translocation. CeU 92, 747-758. 

If the growing polypeptide contains a stop-transfer signal (see p. 228), then this hydro-phobic section of the chain remains stuck in the membrane outside the translocon, and an integral membrane protein arises. In the course of translation, an additional signal sequence can re-start the transfer of the chain through the translocon. Several repetitions of this process produce integral membrane proteins with several transmembrane helices (see p. 214). 

Hagting A, Karlsson C, Clute P, Jackman M, Pines J (1998) MPF localization is controlled by nudear export. EMBO J 17 4127-4138 Hamman BD, Chen JC, Johnson EE, Johnson AE (1997) The aqueous pore through the translocon has a diameter of 40-60 A during cotranslational protein translocation at the ER membrane. Cell 89 535-544 Hampton RY, Rine J (1994) Regulated degradation of HMG-CoA reductase, an integral membrane protein of the endoplasmic reticulum, in yeast. J Cell Biol 125 299-312... 

Pines J (1999) Cell cyde Checkpoint on the nudear frontier. Nature 397 104-105 Plemper RK, Bohmler S, Bordallo ), Sommer T, Wolf DH (1997) Mutant analysis links the translocon and BiP to retrograde protein transport for ER degradation. Nature 388 891-895... 

Liao S, Lin J, Do H, Johnson AE (1997) Both lumenal and cytosolic gating of die aqueous ER translocon pore are regulated from inside the ribosome during membrane protein integration. Cell 90 31-41 Liebman SW, Sherman F (1976) Inhibition of growth by amber suppressors in yeast. Genetics 82 233-249 Liebman SW, Chernoff YO, Liu R (1995) The accuracy center of a eukaryotic ribosome. Biochem Cell Biol... 

Kerscher O, Sepuri NB, Jensen RE (2000) Timl8p is a new component of the Tim54p-Tim22p translocon in the mitochondrial inner membrane. Mol Biol Cell 11 103-116... 

They may enter the cytosol and fold quickly into a compact form. This may require only a few seconds, whereas the translation process in the ribosome may take many seconds. The folding will therefore be cotranslational.525 Depending upon the N-terminal signal peptide the protein may later unfold and pass through a membrane pore or translocon into the endoplasmic reticulum (ER), a mitochondrion, chloro-plast, or peroxisome. Wherever it is, it will be crowded together with thousands of other proteins. It will interact with many of these, and evolution will have enabled some of these to become chaperones (discussed in Chapter 10).526... 

How are the possible choices for newly formed proteins made Much seems to depend upon the amino acid sequences at the ends of the polypeptide chains. As they emerge from a ribosome, some N-terminal signal sequences bind to recognition proteins. One such protein labels the ends of proteins destined for secretion into the vesicles of the ER. This protein ensures that the protein end binds to the signal recognition particle (SRP), enters a translocon pore, and undergoes cotranslational passage into the periplasmic space in bacteria or the ER in eukaryotes. Cotranslational modification reactions also occur both in the... 

Some proteins enter membranes immediately after synthesis. The translocon channel is not required. However, in E. coli an additional protein YidC is needed.603 Homologs of this protein are found in mitochondria (Oxal protein) and in thylakoid membranes of chloroplasts (Alb3 protein).608 These proteins may function in cotranslational insertion. If a protein carries a... 

Figure 29-18 (A) Proposed mechanism for insertion of a loop of polypeptide chain through a translocon pore in a membrane with the positively charged N terminus anchored to the negatively charged inner membrane surface.

I elRnslavemen mlreCTos ADP/ATP translocator TOM/TIM translocon tubular cristae... 

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