Protein biosynthesis

During transcription, a section of DNA encoding a protein, known as a gene, is converted into a molecule called messenger RNA (mRNA).

The ribosomes catalyze the formation of covalent peptide bonds between the encoded amino acids to form a polypeptide chain.

Alternatively, a mutation in the mRNA sequence changes the specific amino acid encoded at that position in the polypeptide chain.

However, in prokaryotes post-transcriptional modifications are not required so the mature mRNA molecule is immediately produced by transcription.

DNA has an antiparallel, double helix structure composed of two, complementary polynucleotide strands, held together by hydrogen bonds between the base pairs.

This property of directionality is due to the asymmetrical underlying nucleotide subunits, with a phosphate group on one side of the pentose sugar and a base on the other.

[1] The enzyme RNA polymerase binds to the exposed template strand and reads from the gene in the 3' to 5' direction.

The proofreading mechanisms allows the RNA polymerase to remove incorrect nucleotides (which are not complementary to the template strand of DNA) from the growing pre-mRNA molecule through an excision reaction.

Therefore, in the pre-mRNA molecule, all complementary bases which would be thymine in the coding DNA strand are replaced by uracil.

[1] In contrast, the 3' Poly(A) tail is added to the 3' end of the mRNA molecule and is composed of 100-200 adenine bases.

[6] During splicing, the intervening introns are removed from the pre-mRNA molecule by a multi-protein complex known as a spliceosome (composed of over 150 proteins and RNA).

[citation needed] During translation, ribosomes synthesize polypeptide chains from mRNA template molecules.

In eukaryotes, translation occurs in the cytoplasm of the cell, where the ribosomes are located either free floating or attached to the endoplasmic reticulum.

The ribosome reads the mRNA molecule in a 5'-3' direction and uses it as a template to determine the order of amino acids in the polypeptide chain.

[12] The ribosome initially attaches to the mRNA at the start codon (AUG) and begins to translate the molecule.

The correct tRNA with the anticodon (complementary 3 nucleotide sequence UAC) binds to the mRNA using the ribosome.

The ribosome then uses its peptidyl transferase enzymatic activity to catalyze the formation of the covalent peptide bond between the two adjacent amino acids.

This process continues with the ribosome moving along the mRNA molecule adding up to 15 amino acids per second to the polypeptide chain.

[6] Termination of the growing polypeptide chain occurs when the ribosome encounters a stop codon (UAA, UAG, or UGA) in the mRNA molecule.

[12] Dr. Har Gobind Khorana, a scientist originating from India, decoded the RNA sequences for about 20 amino acids.

[15] Through post-translational modifications, the diversity of proteins encoded by the genome is expanded by 2 to 3 orders of magnitude.

These proteases are often highly specific and cause hydrolysis of a limited number of peptide bonds within the target protein.

[17] Following translation, small chemical groups can be added onto amino acids within the mature protein structure.

[18] Examples of processes which add chemical groups to the target protein include methylation, acetylation and phosphorylation.

Phosphorylation is the reversible, covalent addition of a phosphate group to specific amino acids (serine, threonine and tyrosine) within the protein.

[16] In glycosylation, a polysaccharide molecule (known as a glycan) is covalently added to the target protein by glycosyltransferases enzymes and modified by glycosidases in the endoplasmic reticulum and Golgi apparatus.

Glycosylation can have a critical role in determining the final, folded 3D structure of the target protein.

In contrast, O-linked glycosylation is the sequential covalent addition of individual sugars onto the oxygen in the amino acids serine and threonine within the mature protein structure.

[22] Patients with sickle cell anemia have a missense or substitution mutation in the gene encoding the hemoglobin B subunit polypeptide chain.

In addition to cancer cells proliferating abnormally, they suppress the expression of anti-apoptotic or pro-apoptotic genes or proteins.

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.
Two strands of DNA separated with an RNA polymerase attached to one of the strands and an RNA molecule coming out of the RNA polymerase
Illustrates the conversion of the template strand of DNA to the pre-mRNA molecule by RNA polymerase.
three strands of RNA at different stages of maturation, the first strand contains introns and exons only, the second strand has gained a 5' cap and 3' tail and contains still introns and exons, the third strand has the cap and tail but the introns have been removed
Outlines the process of post-transcriptionally modifying pre-mRNA through capping, polyadenylation and splicing to produce a mature mRNA molecule ready for export from the nucleus.
Five strands of mRNA with all with a ribosome attached at different stages of translation. The first strand has a ribosome and one tRNA carrying its amino acid base pairing with the mRNA, the second strand has a ribosome and a second tRNA carrying an amino acid base pairing with the mRNA, the third strand has the ribosome catalysing a peptide bond between the two amino acids on the two tRNA's. The fourth strand has the first tRNA leaving the ribosome and a third tRNA with its amino acid arriving. The fifth strand has the ribosome catalysing a peptide bond between the amino acids on the second and third tRNA's with an arrowing indicating the cycle continues
Illustrates the translation process showing the cycle of tRNA codon-anti-codon pairing and amino acid incorporation into the growing polypeptide chain by the ribosome.
A ribosome on a strand of mRNA with tRNA's arriving, performing codon-anti-codon base pairing, delivering their amino acid to the growing polypeptide chain and leaving. Demonstrates the action of the ribosome as a biological machine which functions on a nanoscale to perform translation. The ribosome moves along the mature mRNA molecule incorporating tRNA and producing a polypeptide chain.
three individual polypeptide chains at different levels of folding and a cluster of chains
Shows the process of a polypeptide chain folding from its initial primary structure through to the quaternary structure.
Two polypeptide chain, one chain is intact with three arrows indicating sites of protease cleavage on the chain and intermolecular disulphide bonds. The second chain is in three pieces connected by disulphide bonds.
Shows a post-translational modification of the protein by protease cleavage, illustrating that pre-existing bonds are retained even if when the polypeptide chain is cleaved.
Three polypeptide chains with one amino acid side chain showing, two have a lysine and one has a serine. Three arrows indicating different post-translational modifications with the new chemical group added to each side chain. The first is methylation then acetylation followed by phosphorylation.
Shows the post-translational modification of protein by methylation, acetylation and phosphorylation
Two polypeptide chains, one with an asparagine side chain exposed and a polysaccharide attached to the nitrogen atom within asparagine. The other polypeptide has a serine side chain exposed and the core of a polysaccharide attached to the oxygen atom within serine.
Illustrates the difference in structure between N-linked and O-linked glycosylation on a polypeptide chain.
Formation of a disulfide bond between two cysteine amino acids within a single polypeptide chain and formation of a disulphide bond between two cysteine amino acids on different polypeptide chains, thereby joining the two chains.
Shows the formation of disulphide covalent bonds as a post-translational modification. Disulphide bonds can either form within a single polypeptide chain (left) or between polypeptide chains in a multi-subunit protein complex (right).
two blood curved vessels are shown, on the left one blood vessel contain normal red blood cells throughout the vessel. On the right, the red blood cells have a dish shape due to being sickled, a blockage composed of these distorted red blood cells is present at the curve in the blood vessel.
A comparison between an unaffected individual and an individual with sickle cell anaemia illustrating the different red blood cell shapes and differing blood flow within blood vessels.
Formation of cancerous genes due to malfunction of suppressor genes.