Levels of protein structure, exemplified by haemoglobin and myoglobin

Click on the following links to bring in updated accompanying interactive graphics display files on haemoglobin and myoglobin using Jsmol in a separate window.

Web archaeologists may wish to know that this unit has been through incarnations involving Chime, Java applets and now Jsmol, a javascript based alternative.
I have now altered the table format to make a stab at responsive design format, but left the instructions for Chime users intact!

Primary structure (amino acid sequence)

The haemoglobin  molecule consists of 4 polypeptide (globin) chains. In adults there are 2 alpha chains and 2 beta chains.

alpha chain  (141 amino acid residues):

val  -  leu ser pro ala asp lys thr asn val lys ala ala try gly lys val gly ala his ala gly glu tyr gly ala glu ala leu glu arg met phe leu ser phe pro thr thr lys thr tyr phe pro his phe  -  asp leu ser his gly ser ala  -   -   -   -   -  gln val lys gly his gly lys lys val ala asp ala leu thr asn ala val ala his val asp asp met pro asn ala leu ser ala leu ser asp leu his ala his lys leu arg val asp pro val asp phe lys leu leu ser his cys leu leu val thr leu ala ala his leu pro ala glu phe thr pro ala val his ala ser leu asp lys phe leu ala ser val ser thr val leu thr ser lys tyr arg

beta chain  (146 amino acid residues

val his leu thr pro glu glu lys ser ala val thr ala leu try gly lys val asn   -   -  val asp glu val gly gly glu ala leu gly arg leu leu val val tyr pro try thr gln arg phe phe glu ser phe gly asp leu ser thr pro asp ala val met gly asn pro lys val lys ala his gly lys lys val leu gly ala phe ser asp gly leu ala his leu asp asn leu lys gly thr phe ala thr leu ser glu leu his cys asp lys leu his val asp pro glu asn phe arg leu leu gly asn val leu val cys val leu ala his his phe gly lys glu phe thr pro pro val gln ala ala tyr gln lys val val ala gly val ala asp ala leu ala his lys tyr his

There are many similarities between the sequence of the alpha and beta chains, and - signs above hint at missing sections. Red text :This glutamic acid residue is replaced by valine in sickle cell anaemia (see later).

There is a peptide bond between each amino acid, so they are called residues because -H is removed from each intervening amino group, and -OH from the next -COOH group. At one end of each chain (the N terminal end) is an amino group, and at the other end (the C terminal end) is a carboxylic acid group. 

It is also very interesting to note similarities between the chains of haemoglobin and myoglobin, another protein which is involved in holding and passing on oxygen, but which consists of only one polypeptide chain (with 153 amino acid residues):

val leu ser glu gly glu trp gln leu val leu his val trp ala lys val glu ala asp val ala gly his gly gln asp ile leu ile arg leu phe lys ser his pro glu thr leu glu lys phe asp arg phe lys his leu lys thr glu ala glu met lys ala ser glu asp leu lys lys his gly val thr val leu thr ala leu gly ala ile leu lys lys lys gly his his glu ala glu leu lys pro leu ala gln ser his ala thr lys his lys ile pro ile lys tyr leu glu phe ile ser glu ala ile ile his val leu his ser arg his pro gly asn phe gly ala asp ala gln gly ala met asn lys ala leu glu leu phe arg lys asp ile ala ala lys tyr lys glu leu gly tyr gln gly

Haemoglobin (and myoglobin) produced in other organisms may have a slightly different amino acid sequence, and fewer or extra amino acids, but the next levels of structure are not greatly altered by these variations.

Secondary structure (simple 3D form)

Some of the joined amino acid residues coil to form sections of  alpha helix, due to hydrogen bonds between >N-H and >C=O groups (projecting from peptide bonds of amino acids about 4 residues further along), which stabilises the structure. Other amino acid residues give a turn to the amino acid chains, so the overall structure is fairly compact.



Haemoglobin showing 4 chains A myoglobin molecule for comparison with haemoglobin
If you have chime 2.6, you can click here to see the haemoglobin molecule in a separate browser window. Holding down the left mouse button and moving the mouse (left-drag) will rotate the molecule!
For this view, right click for a menu, then click Display > Ribbons, and  Color > Chain.
You can also click here to see the myoglobin molecule in a separate browser window. Left-drag will rotate the molecule!
For this view, right click for a menu, then click Display > Ribbons, and  Color > Chain.

Tertiary structure

The main bonding involved in stabilising the structure of each haemoglobin chain is the attachment of a haem group  (a porphyrin ring containing iron).

There are no disulphide bridges involved in the tertiary structure of haemoglobin.



Haemoglobin showing 4 chains and haem groups Myoglobin looks similar to a single chain of haemoglobin
Four haem groups (one per polypeptide chain) are shown above in stick mode, each with a yellow iron atom in the centre. In this view, the interaction of the haem group with histidine (projecting from the polypeptide chain) can be visualised.
If you have chime 2.6, you can click here to see the haemoglobin molecule in a separate browser window. Holding down the left mouse button and moving the mouse will rotate the molecule!

For this view, right click for a menu, then click Display > Strands , and  Color > Chain, then Select > Residue > Hem, Display > Sticks, Color > CPK , Select > Atom > Fe, Display > Spacefill > Van der Waals Radii!.

Quaternary structure

Myoglobin does not have a quaternary structure, as it consists of only one polypeptide chain.

Two alpha and two beta chains are associated to form a haemoglobin molecule.
rotating model of haemoglobin molecule
Each haem group can accept a single oxygen molecule,  i.e. 2 atoms, so oxy-hamoglobin holds a maximum of 4 oxygen molecules, i.e 8 atoms. Although we talk of haemoglobin and oxy-haemoglobin as single substances, there are in fact 3 stages between "deoxygenated" and "fully oxygenated" haemoglobin.

Variant forms of haemoglobin

Foetal haemoglobin consists of 2 alpha and 2 gamma chains (quite similar to beta chains).  Foetal haemoglobin has a different affinity for oxygen, and this results in a more efficient transfer of oxygen from the mother's blood to the foetus. After birth, the baby gradually replaces red blood cells containing foetal haemoglobin with those containing adult haemoglobin.

A number of variant forms of haemoglobin are known to be associated with inherited conditions.

Sickle cell anaemia is caused by a small variation in the amino acid structure: a single alteration - substitution of
  valine (non polar) for glutamic acid  (polar) - only in the beta chain - causes the molecule to pack differently into the red blood cells, causing sickling.
This is due to a DNA mutation - a single base substitution - (GAG coding for glutamic acid being replaced by GTG which codes for valine).

Thalassemia is another inherited condition in which reduced production of one of the globin chains occurs
. The unpaired other chain builds up in the cells, resulting in problems.

Key figures

Max Perutz and  John Kendrew: used X ray crystallography to model the molecular structure of haemoglobin and myoglobin
(Nobel prize winners 1962)
Linus Pauling : discovered the alpha-helix (
Nobel Prize in Chemistry in 1954), also investigated sickle cell anaemia
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