Structure of proteins

The structure of the proteins is the composition in amino-acid and conformation in three dimensions of the Protéine S. It describes the position relative of different the Atome S which compose a given protein.

The Protéine S are Macromolécule S of the cell, of which they constitute the " box with outil" , enabling him to digest its food, to produce its energy, to manufacture its components, to move, etc They are composed of a linear sequence of amino-acid bound by peptide connections. This sequence has a three-dimensional organization (or folding up) which is clean for him. Sequence with folding up, there exist 4 levels of structuring of protein.

Primary structure

The primary Structure, or sequence, of a Protéine corresponds to the linear succession of the Amino-acid (or residues) constituting it. The proteins are thus polymeric amino-acids, connected to each other by peptide connections. The primary structure of a protein is the fruit of the translation of the ARNm in proteinic Séquence by the Ribosome. It is thanks to the genetic Code that genetic information (in the form of ARN) is translated into Amino-acid. Concretely, the primary structure is represented by a succession of 20 letters (code 1 letter) different correspondent with the 20 amino-acids.

Polarity, ends N and C-final

The primary sequence of a protein to a well defined direction or polarity. The first amino-acid of the sequence of protein is by convention that which has a free end amine, one speaks about N-final end or N-terminal. In a symmetrical way the last amino-acid is that which has a carboxylate end free, one speaks about C-terminal.

Example of a sequence of amino-acid, l'α-lactalbumine human: MRFFVPLFLVGILFPAILAKQFTKCELSQLLKDIDGYGGIALPELICTMFHTSGYDTQAI VENNESTEYGLFQISNKLWCKSSQVPQSRNICDISCDKFLDDDITDDIMCAKKILDIKGI DYWLAHKALCTEKLEQWLCEKL

There exist experimental methods of determination of the primary structure.

Secondary structure

The secondary Structure describes the local folding up of the principal chain of a protein. The existence of secondary structures comes owing to the fact that foldings up énergétiquement favorable of the peptide chain are limited and that only certain conformations are possible. Thus, a protein can be described by a sequence of amino-acids but also by a sequence of elements of secondary structure.

Moreover certain conformations are definitely favoured because stabilized by hydrogen bonds between the groupings Amide (- NH) and Carbonyle (- CO) of the peptide skeleton. There exist three principal categories of secondary structures according to the scaffolding of hydrogen bonds, and thus according to the folding up of the peptide connections: propellers, layers and elbows.

There exist experimental methods to determine the secondary structure like the nuclear Magnetic resonance, circular dichroism or certain methods of infra-red spectroscopy.

Plane angles and secondary structure

The principal chain contains three covalent bonds per amino-acid. The peptide Connection being a plane connection, it remains two simple connections around whose rotation is possible. One can thus determine the conformation of the skeleton of an amino-acid starting from two plane angles, φ and ψ.

the plane angle φ is defined by the four successive atoms of the skeleton: Co-NH-Cα-CO, the first Carbonyl being that of the preceding residue.
the plane angle ψ is defined by the four successive atoms of the skeleton: NH-Cα-CO-NH, the second Amide being that of the following residue.

All the values of the angles φ and ψ are not possible because some lead to too close contacts between atoms which are very unfavourable énergétiquement. A systematic study of the acceptable combinations of angles φ and ψ was carried out by the biologist and Indian physicist Gopalasamudram Narayana Ramachandran in 1963. He imagined a representation in graphic form of the space (φ, ψ) which bears today the name of diagram of Ramachandran . This diagram shows three principal zones énergétiquement favorable. When one analyzes a structure of protein, one observes that the major part of the amino-acids have combinations of angles (φ, ψ) which are registered inside these zones. The two principal areas correspond to the regular secondary structures which are mainly observed in proteins: the area of the propellers α and that of the layers β. The third area, smaller, corresponds to a left helical conformation (φ>0).

There are two particular amino-acids which make exception to this rule of the diagram of Ramachandran: the Glycine and the Proline. The glycine does not have a side chain (R=H) and, so is much forced in the field of the steric obstruction. It can thus adopt values (φ, ψ) more diversified much, apart from the normally privileged areas. Contrary, the proline is forced: it contains a cycle Pyrrole which empèche rotation corresponding to the angle φ.

Propeller

There is helical conformation when the principal skeleton of protein adopts a periodic helicoid folding up. In the vast majority of the cases, this propeller turns clockwise. She is then known as “right-hand side”. Conversely, when a propeller turns in the anti-clockwise direction, it is known as “left”.

There exist also superhélicoïdaux rollings up where 2 propellers, even more, are rolled up one around the other to form a surperhélice. This type of conformation, or beam of propellers ( coiled-coil ) is not a secondary structure but well a particular type of tertiary structure, present in particular in proteins forming of the fibers ( e.g. Fibrine, Kératine, Myosine).

Propeller α

The propeller α is a very frequent periodic structure in folding up of proteins and peptides. It is characterized by the formation of hydrogen bonds between the grouping Carbonyle - CO of a residue I and the grouping Amide - NH of a residue i+4 . An average turn of propeller α contains 3,6 residues and measurement 0.54 Nm, is a translation of 0.15 Nm per residue. The plane angles φ and ψ of the peptide chain are on average of -57.8° and -47.0° in a propeller α.

In a propeller α, the side chains of the amino-acids are localized in periphery of the propeller and point towards outside (see figure). It is a compact structure, énergétiquement favorable.

The structure of the propeller α was predicted by Linus Pauling and Robert Corey in 1951, starting from theoretical considerations, before being observed indeed for the first time in 1958 in the Myoglobin, the first protein of which the three-dimensional structure was solved by Cristallographie.

Propeller 3₁₀

The propeller 3₁₀ is characterized by the formation of a hydrogen bond between the grouping - CO of a residue I and the grouping - NH of a residue i+3 . An average lead 3₁₀ contains 3 residues and measurement 0.60 Nm, is a translation of 0.2 Nm per residue. The plane angles φ and ψ of the peptide connections are on average of -49.0° and -26.0°. The turn of propeller 3₁₀ is thus narrower and more constrained than that of the propeller α. This type of conformation is not very frequent and its length seldom exceeds 1 to 2 turns.

Propeller π

The propeller π is characterized by the formation of a hydrogen bond between groument the CO of a residue I and grouping NH of a residue i+5 . An average lead π contains 4 residues and measurement 0.50 Nm, is a translation of 0.11 Nm per residue. The plane angles φ and ψ of the peptide connections are on average of -57.1° and -69.7°. The turn of propeller π is thus broader than that of the propeller α. This type of conformation is very rare.

Propeller of the type II

The propellers of the type II are left propellers formed by poly-glycines or poly-prolines. An average step of propeller of the type II contains 3 residues and measurement 0.93 Nm, is a translation of 0.31 Nm per residue. The plane angles φ and ψ of the peptide connections are on average of -79.0° and +145.0°.

Bit and layer β

The bit β is a wide periodic structure. The hydrogen bonds which stabilize it make between distant residues rather than between consecutive residues, as in the case of the propeller α. In fact, a bit β only is not stable. It needs to form hydrogen bonds with other bits β to stabilize itself. One speaks then about layers β. A bit β is a structure of period 2, whose side chains are located alternatively in top and top of the plan of the layer. Caricaturalement, the bit β can be seen like a propeller with a step of 2 amino-acids.

The bits β composing a layer have a polarity, that of the peptide chain which goes from the N-terminal towards the C-terminal. During the fitting of two adjacent bits in a layer, two topologies are possible: either the two bits have the same orientation, or they have opposite orientations. In the first case, one speaks about parallel bits and in the last about antiparallel bits.

The layers β are not plane, they present a crumpling on their surface, with folds alternatively directed upwards and downwards.

Antiparallel layer β

When the bits β are organized in manner head-digs, they form an antiparallel layer β. The groupings - NH and - CO of a residue I of a bit has form hydrogen bonds with the groupings - CO and - NH of a residue J of a bit B . Typically, 2 consecutive bits β connected by an elbow form an antiparallel layer β. An average bit β in an antiparallel layer measures 0.68 Nm, that is to say a translation of 0.34 Nm per residue. The plane angles φ and ψ of the peptide connections are on average of -139.0° and +135.0°.

Parallel layer β

When the bits β all are directed in the same direction, they are formed in a parallel layer β. Thus, 2 consecutive bits β cannot form a parallel layer β. The groupings - NH and - CO of a residue I of a bit has form hydrogen bonds with the groupings - CO of a residue and - NH of a residue j+2 pertaining to a bit B . An average bit β in a parallel layer measures 0.64 Nm, that is to say a translation of 0.32 Nm per residue, the plane angles φ and ψ of the peptide connections are on average of -119.0° and +113.0°.

It should well be noted that a layer β is very often composed of parallel and antiparallel bits. The layers β can be flat but rather tend to form a slightly left structure.

Elbows

The elbows are not periodic structures. It is rather about a particular folding up of the carbonaceous skeleton localized with 3 or 4 consecutive residues. The elbows very often make it possible to connect 2 periodic secondary structures (propellers and/or bits).

Elbows of the type I, II and III

|- | |} In the elbows of the type I, II and III, there is formation of a hydrogen bond between the group - CO of a residue I and the grouping - NH of a residue i+3 . These elbows thus run on 4 residues. It are gathered under the name of elbow β because they often establish the link between 2 bits β. Table 1 recapitulate the privileged angles φ and ψ residues in the center of the elbow.

One can note that an elbow of the type III corresponds to a turn of propeller 3₁₀.

Certain amino-acids tend to be favoured with certain positions of the elbows according to their steric obstruction and/or the plane angles which they can form (see Tableau 2).

There also exists of the elbows of the I' type, II' and III' which is the images mirror of the elbows describes above. Their plane angles are the opposites of those described in Table 1.

Bend γ

In the elbows γ, there is formation of a hydrogen bond between the group - CO of a residue I and the grouping - NH of a residue i+2 . These elbows thus run on 3 residues. The angles φ and ψ of the residue i+1 are of +80.0° and -65.0°, respectively. There exist elbows γ' with plane angles of -80.0° and +65.0°

Other secondary structures

When the local conformation of a proteinic segment does not correspond to any of these secondary structures, it is said that it adopts a conformation in statistical ball not periodical ( random coil ), in opposition to the propellers and with the layers which are periodic structures. This type of structure is generally associated with the loops present between 2 propellers or layers. Winds into a ball statistical does not mean therefore absence of structuring. Thus, certain proteins do not have any element of regular secondary structure (propeller or layer) but have a perfectly stable structure. It is often the case of the hormones and toxins polypeptide.

Tertiary structure

The tertiary structure of a Protéine corresponds to the folding up of the polypeptide chain in space. One speaks more usually about three-dimensional structure, or structure 3D. The structure 3D of a protein is closely related to its function: when this structure is broken by the use of denaturing agent, the protein loses its function: it is denatured.

Dependence of its sequence

The tertiary structure of a protein depends on its primary structure. Thus, two proteins homologous having a strong similiarity with sequence (> 80% of the identical amino-acids) will also have very close structures. The prediction of the tertiary structure starting from the primary structure is at present a very active field of research in Bio-data processing. And of many methods precisely use the homology between proteins to carry out their predictions. It is also known of long time that certain amino-acids support the formation of a secondary structure rather than another. For example, the Proline and the Glycine have a very low propensity has to form propellers α. In fact, many bioinformatic methods of prediction of the secondary structure use only the sequence of proteins to carry out their predictions.

Dependence of its environment

The tertiary structure of a protein also depends on its environment. The local conditions which exist inside each cellular compartment, the solvent, the ionic force, viscosity, the concentration, contribute to modulate conformation. Thus a water soluble protein will need an aqueous environment to adopt its three-dimensional structure. Similarly, a membrane protein will need the hydrophobic environment of the membrane to adopt a conformation.

Hydrophobic effect

The sequence of a protein comprises a certain proportion of amino-acid polar (absorbent) and nonpolar (hydrophobic subjects). Their interactions with the water molecules condition the way in which the polypeptide chain is folded up. The nonpolar amino-acids will tend to avoid water. Conversely the polar residues will seek has to remain near aqueous solvent. Thus, in the case of the soluble proteins, it is formed a hydrophobic heart in the center of the tertiary structure, while the polar groups remain rather on the surface.

In the case of the transmembrane proteins the problem is opposite. The membrane environment is overall hydrophobic. Thus, the absorbent amino-acids will be found in the middle of protein while the hydrophobic amino-acids will be found on the surface. It should be noted that absorbent residues can be found on the membrane surface of proteins, in contact with the hydrophobic medium. In this case, there is strong chance that these residues are implied in interactions with other absorbent residues of same or of another protein.

Proteins intrinsically not-structured

At present, more and more of researchers are interested in the case of proteins intrinsically not structured. They are generally soluble proteins not having a particular structure 3D except when it enter in interaction with autes factors: another protein for example. In fact, this type of proteins is often associated with several function biological, them " souplesse" allowing them to adapt to various interactions. The proteins intinsèquement not structured would account for approximately 10% of the genomes. More generally, approximately 40% of the proteins eucaryotes would have an area intrinsically not structured

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