Protein: Cotranslational and Posttranslational Modification in Organelles


Polypeptides can be modified in the rough endoplasmic reticulum (RER) either during their synthesis (cotranslational) or after the initial synthesis has been completed (posttranslational). These structural modifications are also referred to as protein processing events, which can include N‐linked glycosylation; O‐linked glycosylation; glycolipid attachment; disulfide bond formation to generate secondary structure; modification to fold the polypeptide into a stable tertiary structure (low free energy state) and proteolytic processing of the nascent polypeptide or precursor protein to generate either protein subunits or mature functional protein. Cotranslational and posttranslational modification is therefore critical for generating stable protein structure and ultimately appropriate function. Protein processing is also used to generate appropriate targeting signals, which, following synthesis, are used to traffic each protein to either its correct subcellular compartment or extracellular destination.

Key Concepts:

  • Transcribed mRNA contains the code for polypeptide synthesis, which is exported from the nucleus to the cytoplasm to initiate protein translation.

  • For noncytosolic proteins, the mature mRNA is bound by ribosomes in the cytoplasm, to synthesise a signal sequence, and this complex is then transported to the RER for additional polypeptide synthesis.

  • Newly synthesised polypeptides undergo cotranslational modification in the RER.

  • N‐linked glycosylation is an essential structural component that is added to the nascent polypeptide in the RER and is involved in the initial steps of protein folding.

  • Molecular chaperones in the RER facilitate protein folding to generate correct protein secondary and tertiary structure.

  • There is a quality control process to ensure that only correctly folded and processed proteins exit the RER.

  • Posttranslational modifications can take place in different cellular organelles such as the RER, Golgi, endosomes, lysosomes and secretory vesicles.

  • The Golgi is involved in posttranslational glycoprocessing and the generation of signals for targeting protein to its final destination.

  • Posttranslational proteolytic processing can be used to generate protein subunits and mature functional proteins.

Keywords: ribosomes; polypeptide synthesis; N‐linked glycosylation; O‐linked glycosylation; molecular chaperones; protein folding; quality control in the RER; protein structure; proteolytic processing; intracellular traffic

Figure 1.

Intracellular organelles and protein traffic. A eukaryotic cell and its intracellular organelles, including the nucleus, rough endoplasmic reticulum (RER), Golgi apparatus (cis and trans), secretory vesicles, endosomes and lysosomes. Arrows show the direction of vesicular transport and thus protein traffic (green arrows, the path for the cell surface and secretion; red arrows, the endosome–lysosome pathway). Traffic between the RER and Golgi apparatus is mediated by different coatomer proteins (COP I and COP II), whereas traffic from the Golgi apparatus to the cell surface is mediated by clathrin (shown as a T‐shaped structure on budding membrane).

Figure 2.

Different types of N‐linked oligosaccharide that can be derived from the N‐linked oligosaccharide structures that have been attached to polypeptides in the RER. Adapted from Kornfeld and Kornfeld .

Figure 3.

N‐linked oligosaccharide targeting system, which is required for protein traffic to the lysosomal compartment. (a) Electron micrograph (original magnification, ×20 000) of a human skin fibroblast cell showing a Golgi apparatus, with vesicle formation evident at the termini of the cisternae stacks (arrows). (b) Key enzymes and corresponding sugar structures involved in lysosomal targeting. Squares represent N‐acetylglucosamine sugar residues; circles represent mannose sugar residues and a circled P represents a phosphate moiety. Only soluble proteins with the mannose‐6‐phosphate structure (right) are targeted to lysosomes. Note the removal of the terminal N‐acetylglucosamine sugar residues by a phosphodiester glycosidase (‘uncapping enzyme’), which occurs in the trans‐Golgi network, before lysosomal targeting.



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Shandala, Tetyana, Parkinson‐Lawrence, Emma J, and Brooks, Doug A(Jan 2011) Protein: Cotranslational and Posttranslational Modification in Organelles. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0005716.pub2]