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Protein Primary Sequence

The primary sequence of a protein is the order that the amino acids it contains occur in. Proteins are chains of amino acids which are joined together into a single chain by peptide bonds (Figure 1). The order of the amino acids in the chain is a linear sequence, read along the length of these peptide bonds from the N-terminal (named for the nitrogen atom in an amine group) to the C-terminal (named for the carbon atom in a carboxylic acid group) end of the protein.

A diagram of serine and alanine as individual amino acids on the left, with an arrow to the right, and a peptide bond between them on the right.
Figure 1: The formation of a peptide bond between a serine and an alanine amino acid, the order of these, in this case Ser-Ala is the primary sequence. The carboxyl group of the serine molecule forms a covalent bond with the amine group of the alanine molecule to release a single water molecule, known as condensation polymerisation. A protein is translated from the amine (N) terminus to the carboxyl (C) terminus during synthesis, and the same type of bond is formed between any combination of the 20 amino acids. A protein typically has hundreds or even thousands of amino acids in the primary sequence.

There are 20 amino acids (Table 1), which have a variety of chemical properties. They can be hydrophobic or hydrophilic, acidic, alkaline or neutral, have aromatic rings or be aliphatic, include atoms like sulfur. Proteins, as diverse molecules, have a wide range of properties, and a wide variety of amino acids that can be included to facilitate them.

Table 1: The 20 main amino acids found in proteins. Also given are the amino acid’s 1 and 3 letter codes. 1 letter codes are used in protein sequence databases, and 3 letter codes in often used in scientific literature for brevity. The structures of the amino acids are shown, as well as their chemical formulae. Amino acids are broadly categorized into hydrophobic (which tend to dislike interaction with water), polar (which interact with water, but are uncharged), acidic and basic (which are negatively and positively charged when ionized respectively, and can form electrostatic interactions). Cysteine (forming salt bridges), glycine (being very flexible) and proline (being very rigid) are all characterized as special, as they have unusual properties. Not shown here are some special amino acids, including selenocysteine, which while found in proteins, do not occur in all organisms, and are encoded by unusual mechanisms in the genetic code.
Amino Acid 3 Letter Code 1 Letter Code Type Structure Formula
Alanine Ala A Hydrophobic $\ce{C3H7NO2}$
Cysteine Cys C Special $\ce{C3H7NO2S}$
Aspartic Acid Asp D Acidic $\ce{C4H7NO4}$
Glutamic Acid Glu E Acidic $\ce{C5H9NO4}$
Phenylalanine Phe F Hydrophobic $\ce{C9H11NO2}$
Glycine Gly G Special $\ce{C2H5NO2}$
Histidine His H Basic $\ce{C6H9N3O2}$
Isoleucine Ile I Hydrophobic $\ce{C6H13NO2}$
Lysine Lys K Basic $\ce{C6H14N2O2}$
Leucine Leu L Hydrophobic $\ce{C6H13NO2}$
Methionine Met M Hydrophobic $\ce{C5H11NO2S}$
Asparagine Asn N Polar $\ce{C4H8N2O3}$
Proline Pro P Special $\ce{C5H9NO2}$
Glutamine Gln Q Polar $\ce{C5H10N2O3}$
Arginine Arg R Basic $\ce{C6H14N4O2}$
Serine Ser S Polar $\ce{C3H7NO3}$
Threonine Thr T Polar $\ce{C4H9NO3}$
Valine Val V Hydrophobic $\ce{C5H11NO2}$
Tryptophan Trp W Hydrophobic $\ce{C11H12N2O2}$
Tyrosine Tyr Y Hydrophobic $\ce{C9H11NO3}$

The primary amino acid sequence can be represented as a linear sequence of letters, with each letter representing one amino acid. This has given rise to protein databases, notably the UniProtKB, where such sequences of proteins can be downloaded.

The protein sequence is inherently tied to the DNA sequence associated with it. DNA, transcribed into mRNA and translated into a primary protein sequence linking these three sequences. Each combination of 3 nucleotides (known as codons) encodes a single amino acid, so it is trivial for changes in the DNA sequences to predict changes to the protein primary sequence. It is also easy to store and analyze these sequences using computer algorithms, as they are strings.

The protein primary sequence begins the story of the structure and function of a protein. Next the protein folds into a secondary structure.