Nascent polypeptide-associated

Beatrix, B., Sakai, H., and Wiedmann, M., The alpha and beta subunit of the nascent polypeptide-associated complex have distinct functions, J. Biol Biol, 2000, 275, 37838. 

Figure 13.20 Diagrams for eukaryotic translocations across the ER membrane. The mammalian co-tanslational translocation (a) and yeast post-translational translocation (b) of polypeptide chain are diagrammatically represented. Abbreviations used are SRP, signal recognition particle SR, SRP receptor and TRAM, translocating chain-associated membrane protein. Sec61p spans the ER membrane multiple times and likely forms the translocation channel. The cytosolic components, SsalP and Ydjlp which maintain the nascent polypeptide chain in the unfolded state in the post-translational translocation. The nascent polypeptide-associated complex (NAC) which maintains the fidelity of co-translational precursor and the role of GTP are not shown...

The role of catalysis in membrane assembly is emphasized again by the above model since the N-terminal sequence of the nascent polypeptide chain of a spanning protein is released by proteolysis as soon as it reaches the cytosol. The N-terminal polypeptide chain extension may help the chain penetrate the hydrophobic bilayer and solubilize the resulting hydrophobic N-terminal part of the chain in the aqueous medium of the cytoplasm. However, the role of the protease-catalyzed hydrolysis of the polypeptide chain in membrane assembly is minimized in the membrane trigger hypothesis (99). According to this model, the essential role of the leader sequence would be to modify, in association with the lipid bilayer, the folding pathway of the protein in such a way that the polypeptide chain could span the membrane. 

A unique property of nuclear steroid hormone leceptois is that they associate with a large multicomponent protein complex of chaperones, the Hsp90 (heat-shock protein) system. (Chaperones which associate with nascent polypeptide chains and assist them to fold are named chaperonins, whereas chaperones are proteins which associate with polypeptide chains, post-translationally) (Fig. 11.6). 

It is unlikely that the SRP receptor binds the signal sequence. Association between polysomes and the SRP receptor appears to require the SRP as an intermediary. The extreme basicity of the SRP receptor makes it likely that it binds a highly acidic entity (Lauffer et al., 1985) no part of the signal sequence is acidic. Furthermore, Gilmore and Blobel (1983) have presented evidence that the affinity of the SRP receptor for the ribosome and the nascent polypeptide is low, both in the presence and absence of SRP. 

Figure 3. The oligosaccharide sequence associated with nascent polypeptides.

Ribosomes are high-molecular-weight complexes of RNA (rRNA) and proteins (Table I), and the electron-dense particles are easily visualized by electron microscopy. Ribosomes from various sources (prokaryotes, eukaryotic cytoplasm, mitochondria, chloroplasts, and kinetoplasts) vary in size from 20 to 30 nm in diameter, but all are composed of a large and a small subparticle or subunit and perform similar functions in protein synthesis. The principal functional domains of the ribosome and associated components are given in Fig. 10. More detailed resolution of the ribosome structure has allowed the placement of mRNA, aminoacyl-tRNA, peptidyl-tRNA, and the nascent polypeptide chain (see Section C and Fig. 11). 

In the next stage of N-glycosylation this pre-assembled oligosaccharide is transferred en bloc to an Asn-X-Ser/Thr sequon (where X can be any amino add except Pro or Asp) in the nascent polypeptide chain of a glycoprotein being synthesized at the ribosome (Figures 1 and 2). This co-translational step is catalyzed by the oli-gosaccharyltransferase (OST) complex which consists of at least three proteins [26, 27] that seem to be intimately associated with membrane-bound ribosomes [19]. 

The second step in zinc absorption involves the intracellular interaction of zinc with various compounds which may enhance or impede absorptive processes. In 1969, Starcher noted that radioactive copper, given orally, associated with a low molecular weight protein (25). Subsequently, this mucosal protein was isolated and characterized by Richards and Cousins, who classified it as a metallothionein (26), and who further showed that it was induced in response to zinc administration (5). The appearance of this metallothionein, with properties similar to those described for both rat (27) and human (28) liver metallothionein, appears to be related to changes in both dietary zinc status and plasma zinc levels (5). The synthesis of mucosal metallothionein has been shown to be under transcriptional control (29,30). Menard al. reported that dietary zinc administration resulted in enhancement of metallothionein mRNA transcription and its subsequent translation, to yield nascent metallothionein polypeptides(31). The intestinal metallothionein appearance was correlated to both an increase in mucosal zinc content primarily associated with the protein and with a decrease in serum zinc levels. In addition. Smith e al., using the isolated, vascularly perfused intestinal system, reported an inverse relationship between the synthesis of metallothionein and zinc transfer to the portal system, confirming earlier studies (32). 

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