A protein primary structure is a chain of amino acids.

In biochemistry, the primary structure of a biological molecule is the exact specification of its atomic composition and the chemical bonds connecting those atoms (including stereochemistry). For a typical unbranched, un-crosslinked biopolymer (such as a molecule of DNA, RNA or typical intracellular protein), the primary structure is equivalent to specifying the sequence of its monomeric subunits, e.g., the nucleotide or peptide sequence. The term "primary structure" was first coined by Linderstrom-Lang in his 1951 Lane Medical Lectures. Primary structure is sometimes mistakenly termed primary sequence, but there is no such term, as well as no parallel concept of secondary or tertiary sequence. Description: The Primary structure of a Protein is a chain of Amino acids. ... Description: The Primary structure of a Protein is a chain of Amino acids. ... A representation of the 3D structure of myoglobin, showing coloured alpha helices. ... Phenylalanine is one of the standard amino acids. ... Biochemistry is the study of the chemical processes and transformations in living organisms. ... This article or section does not adequately cite its references or sources. ... In science, a molecule is a group of atoms in a definite arrangement held together by chemical bonds. ... The structure of part of a DNA double helix Deoxyribonucleic acid (DNA) is a nucleic acid that contains the genetic instructions for the development and function of living organisms. ... Ribonucleic acid (RNA) is a nucleic acid polymer consisting of nucleotide monomers, that acts as a messenger between DNA and ribosomes, and that is also responsible for making proteins out of amino acids. ... A representation of the 3D structure of myoglobin, showing coloured alpha helices. ... In chemistry, a monomer (from Greek mono one and meros part) is a small molecule that may become chemically bonded to other monomers to form a polymer. ... A DNA sequence (sometimes genetic sequence) is a succession of letters representing the primary structure of a real or hypothetical DNA molecule or strand, The possible letters are A, C, G, and T, representing the four nucleotide subunits of a DNA strand (adenine, cytosine, guanine, thymine), and typically these are... Peptide sequence or amino acid sequence is the order in which amino acid residues, connected by peptide bonds, lie in the chain. ... Kaj Ulrik Linderstrøm-Lang (Nov. ...

Primary structure of polypeptides

In general, polypeptides are unbranched polymers, so their primary structure can often be specified by the sequence of amino acids along their backbone. However, proteins can become cross-linked, most commonly by disulfide bonds, and the primary structure also requires specifying the cross-linking atoms, e.g., specifying the cysteines involved in the protein's disulfide bonds. Other crosslinks include desmosine... Phenylalanine is one of the standard amino acids. ... A disulfide bond (SS-bond), also called a disulfide bridge, is a strong covalent bond between two sulfhydryl groups. ... Cysteine is a naturally occurring, sulfur-containing amino acid that is found in most proteins, although only in small quantities. ...

The chiral centers of a polypeptide chain can undergo racemization. In particular, the L-amino acids normally found in proteins can spontaneously isomerize at the C^α atom to form D-amino acids, which cannot be cleaved by most proteases. In chemistry racemization refers to partial conversion of one enantiomer into another. ... Proteases (proteinases, peptidases, or proteolytic enzymes) are enzymes that break peptide bonds between amino acids of proteins. ...

Finally, the protein can undergo a variety of posttranslational modifications, which are briefly summarized here. Posttranslational modification is the chemical modification of a protein after its translation. ...

The N-terminal amino group of a polypeptide can be modified covalently, e.g.,

• acetylation − C( = O) − CH₃

The positive charge on the N-terminal amino group may be eliminated by changing it to an acetyl group (N-terminal blocking).

• formylation − C( = O)H

The N-terminal methionine usually found after translation has an N-terminus blocked with a formyl group. This formyl group (and sometimes the methionine residue itself, if followed by Gly or Ser) is removed by the enzyme deformylase.

• pyroglutamate

An N-terminal glutamine can attack itself, forming a cyclic pyroglutamate group.

• myristoylation

Similar to acetylation. Instead of a simple methyl group, the myristoyl group has a tail of 14 hydrophobic carbons, which make it ideal for anchoring proteins to cellular membranes.

The C-terminal carboxylate group of a polypeptide can also be modified, e.g., Image File history File links Nterminal_acetylation. ... Image File history File links Pyroglutamate. ... Drawing of a cell membrane A component of every biological cell, the selectively permeable cell membrane (or plasma membrane or plasmalemma) is a thin and structured bilayer of phospholipid and protein molecules that envelopes the cell. ...

• amidation (see Figure)

The C-terminus can also be blocked (thus, neutralizing its negative charge) by amidation.

• glycosyl phosphatidylinositol (GPI) attachment

Glycosyl phosphatidylinositol is a large, hydrophobic phospholipid prosthetic group that achors proteins to cellular membranes. It is attached to the polypeptide C-terminus through an amide linkage that then connects to ethanolamine, thence to sundry sugars and finally to the phosphatidylinositol lipid moiety.

Finally, the peptide side chains can also be modified covalently, e.g., Image File history File links Cterminal_amidation. ... Drawing of a cell membrane A component of every biological cell, the selectively permeable cell membrane (or plasma membrane or plasmalemma) is a thin and structured bilayer of phospholipid and protein molecules that envelopes the cell. ... The term Side chain can have different meanings depending on the context: In chemistry and biochemistry a side chain is a part of a molecule attached to a core structure. ...

• phosphorylation

Aside from cleavage, phosphorylation is perhaps the most important chemical modification of proteins. A phosphate group can be attached to the sidechain hydroxyl group of serine, threonine and tyrosine residues, adding a negative charge at that site and producing an unnatural amino acid. Such reactions are catalyzed by kinases and the reverse reaction is catalyzed by phosphorylases. The phosphorylated tyrosines are often used as "handles" by which proteins can bind to one another, whereas phosphorylation of Ser/Thr often induces conformational changes, presumably because of the introduced negative charge. The effects of phosphorylating Ser/Thr can sometimes be simulated by mutating the Ser/Thr residue to glutamate.

• glycosylation

A catch-all name for a set of very common and very heterogeneous chemical modifications. Sugar moieties can be attached to the sidechain hydroxyl groups of Ser/Thr or to the sidechain amide groups of Asn. Such attachments can serve many functions, ranging from increasing solubility to complex recognition. All glycosylation can be blocked with certain inhibitors, such as tunicamycin.

• deamidation (succinimide formation)

In this modification, an asparagine or aspartate side chain attacks the following peptide bond, forming a symmetrical succinimide intermediate. Hydrolysis of the intermediate produces either asparate or the β-amino acid, iso(Asp). For asparagine, either product results in the loss of the amide group, hence "deamidation".

• hydroxylation

Proline residues may be hydroxylates at either of two atoms, as can lysine (at one atom). Hydroxyproline is a critical component of collagen, which becomes unstable upon its loss. The hydroxylation reaction is catalyzed by an enzyme that requires ascorbic acid (vitamin C), deficiencies in which lead to many connective-tissue diseases such as scurvy.

• methylation

Several protein residues can be methylated, most notably the positive groups of lysine and arginine. Methylation at these sites is used to regulate the binding of proteins to nucleic acids. Lysine residues can be singly, doubly and even triply methylated. Methylation does not alter the positive charge on the side chain, however.

• acetylation

Acetylation of the lysine amino groups is chemically analogous to the acetylation of the N-terminus. Functionally, however, the acetylation of lysine residues is used to regulate the binding of proteins to nucleic acids. The cancellation of the positive charge on the lysine weakens the electrostatic attraction for the (negatively charged) nucleic acids.

• sulfation

Tyrosines may become sulfated on their O^η atom. Somewhat unusually, this modification occurs in the Golgi apparatus, not in the endoplasmic reticulum. Similar to phosphorylated tyrosines, sulfated tyrosines are used for specific recognition, e.g., in chemokine receptors on the cell surface. As with phosphorylation, sulfation adds a negative charge to a previously neutral site. A phosphorylated serine residue Phosphorylation is the addition of a phosphate (PO4) group to a protein or a small molecule or the introduction of a phosphate group into an organic molecule. ... In biochemistry, a kinase is a type of enzyme that transfers phosphate groups from high-energy donor molecules, such as ATP, to specific target molecules (substrates); the process is termed phosphorylation. ... Phosphorylase is an enzyme that catalyzes the production of glucose phosphate from glycogen and inorganic phosphate. ... Glycosylation is the process or result of addition of saccharides to proteins and lipids. ... Deamidation reaction of Asn-Gly (top right) to Asp-Gly (at left) or iso(Asp)-Gly (in green at bottom right). ... Hydroxylation is any chemical process that introduces one or more hydroxyl groups (-OH) into a compound (or radical) thereby oxidising it. ... Tropocollagen triple helix. ... This article deals with the molecular aspects of ascorbic acid. ... Scurvy (N.Lat. ... Methylation is a term used in the chemical sciences to denote the attachment or substitution of a methyl group on various substrates. ... Acetylation describes a reaction, usually with acetic acid, that introduces an acetyl functional group into an organic compound. ... Diagram of the endomembrane system in a typical eukaryote cell Micrograph of Golgi apparatus, visible as a stack of semicircular black rings near the bottom. ... The endoplasmic reticulum or ER is an organelle found in all eukaryotic cells that is an interconnected network of tubules, vesicles and cisternae that is responsible for several specialized functions: Protein translation, folding, and transport of proteins to be used in the cell membrane (e. ...

• prenylation and palmitoylation

The hydrophobic isoprene (e.g., farnesyl, geranyl, and geranylgeranyl groups) and palmitoyl groups may be added to the S^γ atom of cysteine residues to anchor proteins to cellular membranes. Unlike the GPI and myritoyl anchors, these groups are not necessarily added at the termini. Prenylation or isoprenylation is the addition of hydrophobic molecules to a protein to facilitate its attachment to the cell membrane. ... Drawing of a cell membrane A component of every biological cell, the selectively permeable cell membrane (or plasma membrane or plasmalemma) is a thin and structured bilayer of phospholipid and protein molecules that envelopes the cell. ...

• carboxylation

A relatively rare modification that adds an extra carboxylate group (and, hence, a double negative charge) to a glutamate side chain, producing a Gla residue. This is used to strengthen the binding to "hard" metal ions such as calcium.

• ADP-ribosylation

The large ADP-ribosyl group can be transferred to several types of side chains within proteins, with heterogeneous effects. This modification is a target for the powerful toxins of disparate bacteria, e.g., Vibrio cholerae, Corynebacterium diphtheriae and Bordetella pertussis. General Name, Symbol, Number calcium, Ca, 20 Chemical series alkaline earth metals Group, Period, Block 2, 4, s Appearance silvery white Standard atomic weight 40. ...

• ubiquitination and SUMOylation

Various full-length, folded proteins can be attached at their C-termini to the sidechain ammonium groups of lysines of other proteins. Ubiquitin is the most common of these, and usually signals that the ubiquitin-tagged protein should be degraded. Ubiquitin is a very conserved small regulatory protein that is ubiquitous in eukaryotes. ... Small Ubiquitin-related Modifier or SUMO proteins are a family of small proteins that are covalently attached to and detached from other proteins in cells to modify their function. ...

Most of the polypeptide modifications listed above occur post-translationally, i.e., after the protein has been synthesized on the ribosome, typically occurring in the endoplasmic reticulum, a subcellular organelle of the eukaryotic cell. A representation of the 3D structure of myoglobin, showing coloured alpha helices. ... Figure 1: Ribosome structure indicating small subunit (A) and large subunit (B). ... The endoplasmic reticulum or ER is an organelle found in all eukaryotic cells that is an interconnected network of tubules, vesicles and cisternae that is responsible for several specialized functions: Protein translation, folding, and transport of proteins to be used in the cell membrane (e. ... Schematic of typical animal cell, showing subcellular components. ...

Many other chemical reactions (e.g., cyanylation) have been applied to proteins by chemists, although they are not found in biological systems.

Modifications of primary structure

In addition to those listed above, the most important modification of primary structure is peptide cleavage (See: Protease). Proteins are often synthesized in an inactive precursor form; typically, an N-terminal or C-terminal segment blocks the active site of the protein, inhibiting its function. The protein is activated by cleaving off the inhibitory peptide. Proteases (proteinases, peptidases, or proteolytic enzymes) are enzymes that break peptide bonds between amino acids of proteins. ... The active site of an enzyme is the binding site where catalysis occurs. ...

Some proteins even have the power to cleave themselves. Typically, the hydroxyl group of a serine (rarely, threonine) or the thiol group of a cysteine residue will attack the carbonyl carbon of the preceding peptide bond, forming a tetrahedrally bonded intermediate [classified as a hydroxyoxazolidine (Ser/Thr) or hydroxythiazolidine (Cys) intermediate]. This intermediate tends to revert to the amide form, expelling the attacking group, since the amide form is usually favored by free energy, (presumably due to the strong resonance stabilization of the peptide group). However, additional molecular interactions may render the amide form less stable; the amino group is expelled instead, resulting in an ester (Ser/Thr) or thioester (Cys) bond in place of the peptide bond. This chemical reaction is called an N-O acyl shift.

The ester/thioester bond can be resolved in several ways:

• Simple hydrolysis will split the polypeptide chain, where the displaced amino group becomes the new N-terminus. This is seen in the maturation of glycosylasparaginase.

• A β-elimination reaction also splits the chain, but results in a pyruvoyl group at the new N-terminus. This pyruvoyl group may be used as a covalently attached catalytic cofactor in some enzymes, especially decarboxylases such as S-adenosylmethionine decarboxylase {SAMDC) that exploit the electron-withdrawing power of the pyruvoyl group.

• Intramolecular transesterification, resulting in a branched polypeptide. In inteins, the new ester bond is broken by an intramolecular attack by the soon-to-be C-terminal asparagine.

• Intermolecular transesterification can transfer a whole segment from one polypeptide to another, as is seen in the Hedgehog protein autoprocessing.

Adenosylmethionine decarboxylase is an enzyme which catalyzes the conversion of S-Adenosyl methionine to S-adenosyl-5-3-methylpropylamine. ... An intein is a segment of a protein that is able to excise itself and rejoin the remaining portions (the exteins) with a peptide bond. ...

History of protein primary structure

The proposal that proteins were linear chains of α-amino acids was made nearly simultaneously by two scientists at the same conference in 1902, the 74th meeting of the Society of German Scientists and Physicians, held in Karlsbad. Franz Hofmeister made the proposal in the morning, based on his observations of the biuret reaction in proteins. Hofmeister was followed a few hours later by Emil Fischer, who had amased a wealth of chemical details supporting the peptide-bond model. For completeness, the proposal that proteins contained amide linkages was made as early as 1882 by the French chemist E. Grimaux. Franz Hofmeister (1850-1922) was an early protein scientist, and is famous for his studies of salts that influence the solubility and conformational stability of proteins. ... Hermann Emil Fischer (October 9, 1852 - July 15, 1919) was a German chemist and recipient of the Nobel Prize for Chemistry in 1902. ...

Despite these data and later evidence that proteolytically digested proteins yielded only oligopeptides, the idea that proteins were linear, unbranched polymers of amino acids was not accepted immediately. Some well-respected scientists such as William Astbury doubted that covalent bonds were strong enough to hold such long molecules together; they feared that thermal agitations would shake such long molecules asunder. Hermann Staudinger faced similar prejudices in the 1920s when he argued that rubber was composed of macromolecules. William Astbury (1898-1961) was an English biochemist who made X-ray diffraction studies of nucleic acid in 1937. ... Hermann Staudinger (March 23, 1881 in Worms- Sept. ... Latex being collected from a tapped rubber tree Rubber is an elastic hydrocarbon polymer which occurs as a milky colloidal suspension (known as latex) in the sap of several varieties of plants. ... A macromolecule is a large molecule with a large molecular mass bonded covalently, but generally the use of the term is restricted to polymers and molecules which structurally include polymers. ...

Thus, several alternative hypotheses arose. The colloidal protein hypothesis stated that proteins were colloidal assemblies of smaller molecules. This hypothesis was disproven in the 1920s by ultracentrifugation measurements by The Svedberg that showed that proteins had a well-defined, reproducible molecular weight and by electrophoretic measurements by Arne Tiselius that indicated that proteins were single molecules. A second hypothesis, the cyclol hypothesis advanced by Dorothy Wrinch, proposed that the linear polypeptide underwent a chemical cyclol rearrangement C=O + HN C(OH)-N that crosslinked its backbone amide groups, forming a two-dimensional fabric. Other primary structures of proteins were proposed by various researchers, such as the diketopiperazine model of Emil Abderhalden and the pyrrol/piperidine model of Troensegaard in 1942. Although never given much credence, these alternative models were finally disproven when Frederick Sanger successfully sequenced insulin and by the crystallographic determination of myoglobin and hemoglobin by Max Perutz and John Kendrew. Theodor Svedberg (August 30, 1884 - February 25, 1971) was a Swedish chemist and Nobel laureate. ... Arne Wilhelm Kaurin Tiselius (Stockholm 10 August 1902 – Uppsala 29 October 1971), Swedish biochemist. ... Please wikify (format) this article or section as suggested in the Guide to layout and the Manual of Style. ... Dorothy Maud Wrinch (married names Nicholson, Glaser) (September 12, 1894 - February 11, 1976) was a mathematician and biochemical theorist best known for her attempt to explain protein structure using mathematical principles. ... Emil Abderhalden (9 March 1877 - 5 August 1950) was a Swiss biochemist and physiologist. ... Frederick Sanger, OM, CH, CBE, FRS (born 13 August 1918) is an English biochemist and a two time Nobel laureate in Chemistry. ... Insulin (from Latin insula, island, as it is produced in the Islets of Langerhans in the pancreas) is a polypeptide hormone that regulates carbohydrate metabolism. ... Max Ferdinand Perutz, OM (May 19, 1914 – February 6, 2002) was an Austrian-British molecular biologist. ... This article or section does not cite its references or sources. ...

Relation to secondary and tertiary structure

The primary structure of a biological polymer to a large extent determines the three-dimensional shape known as the tertiary structure, but nucleic acid and protein folding are so complex that knowing the primary structure often doesn't help either to deduce the shape or to predict localized secondary structure, such as the formation of loops or helices. However, knowing the structure of a similar homologous sequence (for example a member of the same protein family) can unambiguously identify the tertiary structure of the given sequence. Sequence families are often determined by sequence clustering, and structural genomics projects aim to produce a set of representative structures to cover the sequence space of possible non-redundant sequences. In biochemistry, the tertiary structure of a protein is its overall shape. ... Look up nucleic acid in Wiktionary, the free dictionary. ... Protein folding is the process by which a protein assumes its characteristic functional shape or tertiary structure, also known as the native state. ... A representation of the 3D structure of the Myoglobin protein. ... In biology, homology is any similarity between structures that is due to their shared ancestry. ... A protein family is a group of evolutionarily related proteins. ... In biochemistry, the tertiary structure of a protein is its overall shape. ... In bioinformatics, sequence clustering algorithms attempt to group sequences that are somehow related. ... Structural genomics or structural bioinformatics refers to the analysis of macromolecular structure particularly proteins. ...

Primary structure in other molecules

Any linear-chain heteropolymer can be said to have a "primary structure" by analogy to the usage of the term for proteins, but this usage is rare compared to the extremely common usage in reference to proteins. In RNA, which also has extensive secondary structure, the linear chain of bases is generally just referred to as the "sequence" as it is in DNA (which usually forms a linear double helix with little secondary structure). Other biological polymers such as polysaccharides can also be considered to have a primary structure, although the usage is not standard. Ribonucleic acid (RNA) is a nucleic acid polymer consisting of nucleotide monomers, that acts as a messenger between DNA and ribosomes, and that is also responsible for making proteins out of amino acids. ... A representation of the 3D structure of the Myoglobin protein. ... The structure of part of a DNA double helix Deoxyribonucleic acid (DNA) is a nucleic acid that contains the genetic instructions for the development and function of living organisms. ... Polysaccharides (sometimes called glycans) are relatively complex carbohydrates. ...

See also

• secondary structure
• tertiary structure
• quaternary structure
• protein sequencing
• translation

A representation of the 3D structure of the Myoglobin protein. ... In biochemistry, the tertiary structure of a protein is its overall shape. ... In biochemistry, many proteins are actually assemblies of more than one protein (polypeptide) molecule, which in the context of the larger assemblage are known as protein subunits. ... Proteins are found in every cell and are essential to every biological process, protein structure is very complex: determining a proteins structure involves first protein sequencing - determining the amino acid sequences of its constituent peptides; and also determining what conformation it adopts and whether it is complexed with any... Translation is the second process of protein biosynthesis (part of the overall process of gene expression). ...

References

• Iwai K and Ando T. (1967) "N O Acyl Rearrangement", Methods Enzymol., 11, 263-282.

• Perler FB, Xu MQ and Paulus H. (1997) "Protein Splicing and autoproteolysis mechanisms", Curr. Opin. Chem. Biol., 1, 292-299.

• Paulus H. "The chemical basis of protein splicing", Chem. Soc. Rev., 27, 375-386.

• Hofmeister F. (1902) Naturwiss. Rundschau, 17, 529-545.

• Fischer E. (1902) Autoreferat. Chem. Ztg., 26, 93.

• Troensegaard N. (1942) Über die Struktur des Proteinmoleküls: eine chemische Untersuchung. E. Munksgaard, København (Copenhagen).

• Sanger F. (1952) "The arrangement of amino acids in proteins", Adv. Protein Chem., 7, 1-67.

• Fruton JS. (1979) "Early theories of protein structure", Ann. N.Y. Acad. Sci., 325, 1-18.

• Wieland T and Bodanszky M (1991) The World of Peptides, Springer Verlag. ISBN 0-387-52830-X