Protein biosynthesis

A nucleus within a cell showing DNA, RNA and enzymes at the different stages of protein biosynthesis
Protein biosynthesis starting with transcription and post-transcriptional modifications in the nucleus. Then the mature mRNA is exported to the cytoplasm where it is translated. The polypeptide chain then folds and is post-translationally modified.

Protein biosynthesis (or protein synthesis) is a core biological process, occurring inside cells, balancing the loss of cellular proteins (via degradation or export) through the production of new proteins. Proteins perform a number of critical functions as enzymes, structural proteins or hormones. Protein synthesis is a very similar process for both prokaryotes and eukaryotes but there are some distinct differences.[1]

Protein synthesis can be divided broadly into two phases: transcription and translation. During transcription, a section of DNA encoding a protein, known as a gene, is converted into a template molecule called messenger RNA (mRNA). This conversion is carried out by enzymes, known as RNA polymerases, in the nucleus of the cell.[2] In eukaryotes, this mRNA is initially produced in a premature form (pre-mRNA) which undergoes post-transcriptional modifications to produce mature mRNA. The mature mRNA is exported from the cell nucleus via nuclear pores to the cytoplasm of the cell for translation to occur. During translation, the mRNA is read by ribosomes which use the nucleotide sequence of the mRNA to determine the sequence of amino acids. The ribosomes catalyze the formation of covalent peptide bonds between the encoded amino acids to form a polypeptide chain.[citation needed]

Following translation the polypeptide chain must fold to form a functional protein; for example, to function as an enzyme the polypeptide chain must fold correctly to produce a functional active site. To adopt a functional three-dimensional shape, the polypeptide chain must first form a series of smaller underlying structures called secondary structures. The polypeptide chain in these secondary structures then folds to produce the overall 3D tertiary structure. Once correctly folded, the protein can undergo further maturation through different post-translational modifications, which can alter the protein's ability to function, its location within the cell (e.g. cytoplasm or nucleus) and its ability to interact with other proteins.[3]

Protein biosynthesis has a key role in disease as changes and errors in this process, through underlying DNA mutations or protein misfolding, are often the underlying causes of a disease. DNA mutations change the subsequent mRNA sequence, which then alters the mRNA encoded amino acid sequence. Mutations can cause the polypeptide chain to be shorter by generating a stop sequence which causes early termination of translation. Alternatively, a mutation in the mRNA sequence changes the specific amino acid encoded at that position in the polypeptide chain. This amino acid change can impact the protein's ability to function or to fold correctly.[4] Misfolded proteins have a tendency to form dense protein clumps, which are often implicated in diseases, particularly neurological disorders including Alzheimer's and Parkinson's disease.[5]

  1. ^ Alberts B (2015). Molecular biology of the cell (Sixth ed.). Abingdon, UK: Garland Science, Taylor and Francis Group. ISBN 978-0815344643.
  2. ^ O'Connor C (2010). Essentials of Cell Biology. NPG Education: Cambridge, MA. Retrieved 3 March 2020.
  3. ^ Wang YC, Peterson SE, Loring JF (February 2014). "Protein post-translational modifications and regulation of pluripotency in human stem cells". Cell Research. 24 (2): 143–160. doi:10.1038/cr.2013.151. PMC 3915910. PMID 24217768.
  4. ^ Scheper GC, van der Knaap MS, Proud CG (September 2007). "Translation matters: protein synthesis defects in inherited disease". Nature Reviews. Genetics. 8 (9): 711–723. doi:10.1038/nrg2142. PMID 17680008. S2CID 12153982.
  5. ^ Berg JM, Tymoczko JL, Gatto Jr GJ, Stryer L (2015). Biochemistry (Eighth ed.). US: W. H. Freeman and Company. ISBN 9781464126109.

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