Primary Structure of Proteins


As described in a previous post, four levels of organization have been distinguished in the structure of proteins:

 

 

The primary structure of proteins is the sequence of amino acids in a polypeptide chain, linked through peptide bonds, that form the covalent backbone of the proteins. The sequence of amino acids is read from the N-terminal amino acid to the C-terminal amino acid.

 

It is important to realize that two proteins that have the same amino acid composition, can have very different primary structure. These two peptides, for example (a peptide is a short amino acid chain formed by a few amino acids), are formed by the same amino acids, but their primary structure is different, since the sequence is different.

 

H2N-Glu-Ala-Val-Ser-Leu-Ala-Lys-Cys-COOH

H2N-Ala-Glu-Val-Ser-Ala-Leu-Lys-Cys-COOH

 

The primary structure determines the three-dimensional structure of the protein, which in turns determines its biological function. Alteration in normal primary structure of proteins can produce catastrophic results.

 

The peptide bond:

 

The peptide bond is a type of carbamide linkage.

 

An amide linkage is a bond between an acid and an amine. There are phosphamide linkages, if the acid is phosphoric acid, sulfamide linkages, if the acid is sulphuric, etc. A carbamide linkage in an amide linkage in which the acid that participates is a carboxylic acid.

 

 

A peptide bond is a kind of carbamide linkage, in which the carboxyl group belongs to one amino acid and the amine group belongs to other amino acid:

 

 

Features of the peptide bond

 

1.- It has the characteristic of a partial double bond between the carbon of the carbonyl group and the N from the amino group, so the bond order is 1.5; it means that it is not a rotating bond as single bonds, but it is rigid. It is said that the bond order is 1.5, to contrast to the bond order of 1, for single bonds, and bond order of 2 for double bonds.

 

Since the six atoms that form the peptide bond are in the same plane, and this bond is rigid, it would appear that it is possible to have trans and cis configuration, but in fact the configuration in the peptide bond is always trans.

 

Alterations in primary structure of the proteins may be unnoticed or may produce catastrophic results.

 

In some cases, a mutation change an amino acid for a very similar one, withour affecting higher structures or functions of the protein. It is called a Conservative Mutation. An example of this kind of mutations could be the change of an apolar amino acid for another apolar amino acid, or an acidic amino acid for another acidic amino acid, lile Asp for Glu.

 

In other cases, a mutation results in the change of an amino acid for other, usually a very different one, affecting higher structures or functions of the protein, ex. an apolar amino acid for a polar amino acid, or a negative charged by a positively charged, etc. This kind of mutation is called a Non-conservative mutation.

 

There has been described hundreds of mutations that affect hemoglobin. In some cases, the change of amino acid in the primary structure has been discovered by chance, since the mutation does not have cinical significance.

 

In other cases, the mutations produce important clinical signs. The most important example is Sickle cell anemia.

 

 

The sickle cell syndromes are caused by a mutation in the Beta-globin gene of hemoglobin that changes the sixth amino acid in the Beta-chain, from glutamic acid to valine

 

Type of Hemoglobin

Codons 5-6-7

Amino acids 5-6-7

 Hemoglobin A (normal)

CCU-GAG-GAG

Pro-Glu-Glu

Hemoglobin S (Sicklemia)

CCU-GUG-GAG

Pro-Val-Glu

 

 

This small change in the primary structure puts a hydrophobic amino acid on the outside of the molecule. This hydrophobic area causes the attachment of adjacent hemoglobins when the globin molecule shifts in conformation following the release of oxygen.

The attached hemoglobin will form then polymeric chains that produce polymerized rods of liquid crystalline hemoglobin. These polymers stiffen the red blood cell membrane, increasing viscosity and causing dehydration. As a consequence of these changes, the characteristic sickle shape appears

 

 

Sickled cells lose the pliability needed to pass through small capillaries, and it provokes episodes of microvascular vasoocclusion and premature erythrocyte destruction (hemolytic anemia).

 

 

In fact, the discovery of the relationship between this small change in the primary structure of Hemoglobin and the signs and symptoms of Sickle Cell anemia, was a milestone in the development of Medical Biochemistry, Genetics and Molecular Biology, and introduced forever the expression “molecular disease”

 

More information can be found in the following links:

 

Primary structure of Proteins

 

http://www.elmhurst.edu/~chm/vchembook/565proteins.html

 

http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/P/PrimaryStructure.html

 

http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/P/Polypeptides.html

 

Peptide bond

http://en.wikipedia.org/wiki/Peptide_bond

 

Different kinds of Hemoglobin:

http://www.scinfo.org/hemoglb.htm

 

Structure-function relations of human hemoglobin

http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1484532

 

Hemoglobinopathies

 

 

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6 thoughts on “Primary Structure of Proteins

  1. Pingback: Protein Structure: Overview « The Biochemistry Questions Site

  2. Pingback: Extended Match Question about Protein Structure. « The Biochemistry Questions Site

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