Nascent polypeptide-associated complex

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...

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). 

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]. 

There is also preliminary evidence for a protein secretion apparatus in Bacillus subtilis. Caulfield et al. (1984, 1985) have studied the S complex, a particle consisting of four proteins that appears to be involved in protein secretion. The complex is present on ribosomes as a small particle, essentially a third ribosomal subunit its proteins can be cross-linked to the 50 S ribosomal subunit. In addition, a 64-kDa protein present in the S complex is protected from added protease in the presence of both ribosomes and membrane, but not by either alone. The S complex does not appear to cause an arrest of translation (Caulfield et al., 1984). The S complex aggregates to form a clathrin-like structure when it is removed from ribosomes (Caulfield et al., 1985). The authors have proposed that such a structure might serve to form a cage around a nascent secretory polypeptide, isolating it from the cytoplasm until it reaches the membrane. Subsequent to membrane binding, three of the proteins of the S complex dissociate and the 64-kDa protein remains associated. This latter protein may then play a role in secretion. 

UAA and UGA RF-3 enhances the activities of RF-1 and RF-2. Codon-bound RF-1 and RF-2 cause a change in the catalytic activity of peptidyl-transferase so that the nascent peptide may be transferred to a molecule of water. This causes the carboxyl end of the growing polypeptide chain to be freed from its anchor, tRNA, and released from the ribosome which dissociates into 30S and SOS subunits. The subunits are held apart by association of IF-3 with the 30S subunit. The mechanism of protein synthesis appears to be highly complex. This degree of complexity is believed to have evolved to achieve the accuracy commensurate with the maintenance of the fidelity of protein synthesis. 

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