Protein: Cotranslational and Posttranslational Modification in Organelles

Abstract

AbstractPolypeptides 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 includeN‐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.