= Protein primary structure
{wiki}
The <protein primary structure> specifies the ordered <amino acid residues> of each <polypeptide chain>, joined through <peptide bonds>. A chain is conventionally written from its <N-terminus> to its <C-terminus>. In the broader chemical sense, a complete <protein primary structure> also specifies <covalent bond> crosslinks between chain positions, including <protein disulfide bonds>; a bare sequence string leaves that information unstated. This describes chemical connectivity rather than the spatial arrangement of <protein tertiary structure> or <protein quaternary structure>. See https://goldbook.iupac.org/terms/view/P04843[IUPAC Gold Book: primary structure, sequence and chain crosslinking] and https://iupac.qmul.ac.uk/AminoAcid/A1416.html[IUPAC-IUB, 3AA-16: writing residue sequences from the amino end]. Some conventions reserve <protein primary structure> for sequence alone and call the complete chemical connectivity the covalent structure; the distinction should be stated when comparing descriptions. See https://iupac.qmul.ac.uk/misc/noGreek/ppep4.html[IUPAC-IUB polypeptide-conformation recommendations, section 6.1: the narrower sequence-only convention].
\Image[/protein-primary-sequence-composition.png]
{title=Equal <amino acid composition> and equal termini do not determine <protein primary structure>}
{description=Original toy <polypeptide chains> MAGAMG and MMAAGG, read from the <N-terminus> to the <C-terminus>. Each contains two <methionine>, two <alanine> and two <glycine> <amino acid residues>, but their internal order differs. Letters denote chain positions rather than free <amino acids>; lines denote <peptide bonds>. Neither string is identified as a natural <protein> or a measured sequence.}
In this toy example M denotes <methionine>, A <alanine> and G <glycine>. Both <polypeptide chains> have six <amino acid residues>, five <peptide bonds>, an M at the <N-terminus> and a G at the <C-terminus>. Their <amino acid composition> is identical, yet position 2 is A in MAGAMG and M in MMAAGG. There are $6!/(2!2!2!)=90$ distinct orders with these counts, a <multinomial coefficient>. Even fixing those two end residues leaves $4!/(1!2!1!)=12$ orders. The counts constrain the answer without determining it.
For multiple <polypeptide chains>, record each sequence separately and specify any <protein disulfide bonds> between <cysteine> positions. Mature <insulin>, for example, has an A chain of 21 <amino acid residues> and a B chain of 30 <amino acid residues>. Their combined 51 residues give $(21-1)+(30-1)=49$ <peptide bonds>, rather than the 50 of one unbroken 51-residue chain. See https://www.ncbi.nlm.nih.gov/books/NBK9879/[Cooper, The Cell: insulin's two chains and cysteine crosslinks, figure 2.16]. A <protein disulfide bond> joins side groups; it does not concatenate the <C-terminus> of one chain with the <N-terminus> of another. The three <insulin> <protein disulfide bonds> connect A6 to A11 within the A chain, and A7 to B7 and A20 to B19 between chains. Positions are numbered from each chain's <N-terminus>. See https://pubmed.ncbi.nlm.nih.gov/15653430/[Replacement of the interchain disulfide bridge-forming amino acids A7 and B7 by glutamate impairs the structure and activity of insulin: native disulfide positions].
Why keep this information? <Protein primary structure> lets us distinguish changes of chemical identity from changes of shape, and compare corresponding positions between <proteins>. <Protein folding> can bring distant <amino acid residues> together at a <protein binding site> while preserving their sequence. The attractive idea is that a readable linear record can constrain a complicated three-dimensional object; it is not, by itself, a guarantee of a unique fold in every environment. See <protein folding> and the <ribonuclease A refolding experiment>. Merely bending an intact chain preserves its <protein primary structure>; <hydrolysis> of a <peptide bond>, or changing which positions a <protein disulfide bond> connects, changes its chemical connectivity.
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