Structure of Proteins (With Diagram) | Biochemistry

In this article we will discuss about the various structures of proteins. This will also help you to draw the structure and diagram of proteins.

Proteins consist of long polypeptide chains and we know how to determine the sequence of the amino acids of these chains. This constitutes the primary structure of proteins. But in reality, each protein has a three-dimensional structure of its own, established and maintained by types of linkages other than the peptide linkage.

It is said that the “native” protein has a secondary, tertiary and even quaternary structure in certain cases, but before considering these different structures, one must understand the interactions which make them possible.

Bonds Involved in the Spatial Structure of Proteins:

A. Disulphide Bond (or Disulphide Bridge):

The covalent bond (strong bonding) between two residues of cysteine belonging to either the same peptide chain or two different chains (see formula of insulin, fig. 1-14).

B. Ionic Bond (or Saline Bond):

It is a non-covalent (therefore weaker), electrovalent bond between a posi­tively charged radical (-NH₃⁺, or = NH₂⁺, for example) and a negatively charged radical (— COO^–, for example) joining two parts of the same chain or two different chains.

This type of interaction even permits the bonding be­tween two different molecules in heteroproteins (for example, in nucleoproteins, between the negatively charged nucleic acid and the positively charged basic proteins, especially the histones).

C. Hydrogen Bond:

This type of non-covalent bond is formed when we have in close proximity, on the one hand, one hydrogen atom bonded to a nitrogen atom or to an oxygen atom and on the other hand, the unshared electronic doublet of another nitrogen atom or oxygen atom.

These bonds can form:

1. Between the > C = O and the > N – H of peptide linkages;

2. Between the radicals of amino acid residues and involve for example, the phenolic group of tyrosine, the imidazole nucleus of histidine, the γ -carboxyl group of glutamic acid, the amide group of asparagine or glutamine.

We will see that the hydrogen bonds can either be intra-chain and maintain the helicoidal conformation of the chain, for example, or can produce inter-­chain interactions.

D. Hydrophobic Bond:

Certain amino acids have a non-polar hydrophobic side chain (Ala, Val, Leu, He, Phe) which does not form any hydrogen bond with water molecules (which associate through hydrogen bonds): these side chains thus repelled tend to get closer to each other, leading to interactions between different parts of a peptide chain (these interactions are of the Van der Waals type).

Secondary Structure of Proteins:

X-ray diffraction patterns provided the data for this structural study. There are generally two main types of secondary structure: the stretched state and the helicoidal state.

Before describing these two states we will review the spatial properties of the peptide linkage.

A. Spatial Properties of the Peptide Bond:

The peptide linkage can in fact, be written in two ways (mesomeric forms):

It has therefore a double bond character which implies that all atoms (C_α, C, O, N, H and C_α) are coplanar. Besides, there is a possibility of cis-trans isomerism for the two carbon atoms C_α and C_α with respect to this linkage. In natural peptides and proteins one mainly finds the plane trans configuration.

These properties give three possibilities of spatial arrangements for the planes formed by successive peptide linkages of a peptide chain:

i. The successive planes alternate in two privileged spatial orientations forming a pleated sheet structure;

ii. The successive planes rotate regularly, always in the same direction, giving a structure of the helicoidal type;

iii. Lastly, the planes can rotate at random. The resulting structure is said to be random coil.

The tetrahedral c_α atoms are always situated at the hinge of two consecutive planes.

B. Stretched State or Pleated Sheet Structure:

The fibrous proteins, or scleroproteins, often found as structural proteins (β-keratin, silk fibroin) have this type of conformation, represented in figure 1-17. We see two antiparallel polypeptide chains (“moving” in opposite direc­tions) united by interchain hydrogen bonds.

The atoms of the peptide linkage are situated in the same plane, but the α carbon atoms belong simultaneously to two different planes. Periodicity is of the order of 7Å (7 x 10^-7 mm).

C. Helicoidal State or α-Helix:

The α-helix is shown in figure 1-18. It is seen that the peptide chain is maintained in this helicoidal configuration by intra-chain hydrogen bonds. The helix has 3.7 amino acid residues per turn. The planes of peptide linkages form between them an angle of about 80° (the intersection of the 2 planes is always at the α carbon). The side chains are directed outwards and can react with each other or with the medium.

If a fiber of a-keratin of helicoidal structure is stretched, β-keratin in pleated sheets is obtained.

Several α-helices can coil round one another like a twisted, twined cable, forming fairly voluminous and strong fibers due to numerous disulphide and hydrogen bonds.

The figure shows a left-handed helix, but very often, natural proteins contain right-handed helices.

D. Random Coil:

Contrary to the two previous states this is a non-ordered state. The peptide chain has no regular geometrical form in space, but the valency angles are however always respected.

E. β Turn:

This is a special structure involving 4 residues of amino acids represented in the diagram below: the α-carbon atoms are numbered 1, 2, 3 and 4. A hydrogen bond is formed between the CO group of the first residue and the NH group of the fourth. In these conditions the sequence portions preceding and following this β turn are antiparallel.

Tertiary Structure of Proteins:

Globular proteins or spheroproteins which form the majority of biologically active proteins (especially the enzymes) are, as indicated by their name, more compact than those mentioned above. They may consist of several chains; they may also consist of a single polypeptide chain having, at some places, zones in a-helix and at some others, zones of less regular curvatures and folds.

The percentage of a-helix varies considerably among the proteins and depends on their primary structure: certain amino acids, especially proline, have a struc­ture which breaks the regularity of the α-helix.

The study of high resolution (of the order of 2Å) X-ray diffraction patterns has revealed the tertiary structure of certain proteins. The first tertiary structures were determined by Kendrew and Perutz for myoglobin and hemoglobin. Figure 1-19 represents the tertiary structure of globin (protein part of myoglobin).

The tertiary structure is of capital importance for the biological activity of proteins. Residues of amino acids very distant from one another in the se­quence, can be brought very near due to the folding and thus form regions indispensable for the functioning of the protein, for example the active site (or catalytic site) of enzymes.

The polar side chains are often grouped on the surface, while the hydrophobic radicals, joined by bonds of the same kind which can be mostly pushed inside the protein structure.

Thanks to the groups accessible on the surface, the protein can link with different protein or non-­protein compounds provided there is a certain complementarity, i.e. a certain steric compatibility. This leads us to consider a last aspect of complexity in the structure of proteins.

Quaternary Structure of Proteins:

Several polypeptide chains can combine in a specific manner. Very often, biological activity exists only in the oligomer (dimer, tetramer, etc.) and not in the protomer. The interactions allowing the association of these polypeptide sub-units are those we studied earlier; they are thus involved in the estab­lishment of the quaternary as well as secondary and tertiary structures.

In certain cases, the quaternary structure results from the assembly of identical peptide units, and in other cases from the assembly of different sub-units. For example, hemoglobin which has to transport oxygen from the lungs to different tissues, consists of 4 sub-units, generally 2 α-chains and 2 β-chains; each of these chains has a tertiary structure similar to the one shown in figure 1-19.

There are also many enzymes which consist of sub-units; in particular, we will see that enzymes whose activity is subjected to an allosteric regulation, consist of sub-units with a very different structure and role.

Lastly, the notion of quaternary structure may be extended to hetero- proteins, formed by the association of protein and non-protein sub-units. Hence, a viral particle in which a nucleic acid and a protein are linked, may be considered as constituting a heterogeneous quaternary structure.