Protein Primary Structure

Abstract

Abstract The order of the amino acids in a polypeptide chain is referred to as its amino acid sequence or primary structure. It is specified by the nucleotide sequence of the encoding gene, and it is assembled in cells through the process called translation. The primary structure determines the shape into which a polypeptide chain naturally folds, and consequently allows its biochemical function. But highly regulated enzymatic activities in cells can drive the recoding of nucleotide messages. Moreover, after or even during the biosynthesis, specific amino acid residues often undergo specific chemical modifications. These posttranslational modifications, able to modulate the physical and chemical properties, folding, stability and ultimately the function of the polypeptide chains, are considered as features of the primary structure of proteins. A large community of scientists has been dedicated to setting up complementary methods to determine this first level in the hierarchical order of the protein structure. Thanks to these methodological efforts, millions of protein primary structures have been determined to date and deposited in large public specialised databases freely accessible for structural and evolutionary relationship studies. Key Concepts Proteins are built up from l‐alpha amino acid units The amino acid linear arrangement determines the 3D structure and consequently the biochemical function of a protein Amino acids are polymerised to a unique sequence by a biosynthetic process, according to which a nucleotide sequence is translated into an amino acid sequence Recoding activities have been known, leading to alternative protein products in a regulated and controlled process Posttranslational modifications can additionally modify an amino acid sequence to drive a sophisticated modulation of conformation and function of proteins Biotechnological production of therapeutic proteins demands a highly accurate verification of the primary structure of products Depending on the genome information available, the determination of the protein primary structure can be accomplished either by direct methods on isolated or partially resolved proteins or by the indirect deciphering of their nucleic acid sequences