Last modified 19th May '95 © Birkbeck College 1995

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Part 1; Part 3

Allostery: Haemoglobin (part 2)- Structure

The subunits of haemoglobin

The alpha and beta subunits are homologous. They have the standard globin fold, but the alpha chains have one fewer helix than the beta chains or myoglobin : the D helix is replaced by a loop region. Here is a diagram of the haemoglobin fold. (Compare this to the myoglobin fold.) Examine the structure of a single subunit (alpha); the myoglobin structure is here .

The Haem Prosthetic Group

Haem (Fe-protoporphyrin IX) consists of a porphyrin ring with an iron atom bound to the four nitrogens at the centre.

Click here for a diagram of haem.

The haem group is situated between helices E and F, and is surrounded by non-polar residues except for the two carboxylate groups exposed at the protein surface (here is a diagram, and for two histidines. One of these (His 87 in alpha subunit, His 92 in beta), part of helix F, binds directly to the iron atom of the haem group (the NE2 atom of the His side chain occupies one of the six coordination positions of the iron). This His is in each subunit called the proximal histidine. The distal histidine occurs in helix E (His 58 in alpha subunit, His 63 in beta). This is near to the opposite coordination position, but does not occupy it; this coordination site is occupied by oxygen in oxyhaemoglobin.

Here are orthogonal views of (oxy)haemoglobin illustrating the positions of the proximal and distal histidines in relation to the haem.

Quaternary structure

The orientation of the four subunits in the tetrameric haemoglobin molecule is indicated in this diagram.

Swiss-3D prot provide this diagram.

Deoxyhaemoglobin: the T state

A number of salt bridges occur in the Tense state which are broken in the Relaxed state:
  1. The carboxyl terminus group (residue Arg 141) of each alpha subunit makes a salt bridge with the amino terminus group (residue Val 1) of the other alpha subunit
  2. The side chain of the Arg 141 C-terminal residue of each alpha subunit interacts with the Asp 126 side chain of the other alpha subunit
  3. Lys 40 of each alpha subunit salt bridges with the C-terminus group (residue His 146) of the beta subunit of the other "dimer"; i.e. Lys 40 of alpha 1 interacts with C-terminus of beta 2.
  4. The side chain of the His 146 C-terminal residue of each beta subunit interacts with Asp 94 of the same chain.

This diagram illustrates (1) and (2) of the above.

This diagram illustrates (3) and (4).

These interactions may also be examined in this structure which includes side chains only for the residues mentioned above .

Here is the complete structure of deoxyhaemoglobin.

The haem group of deoxyhaemoglobin is domed rather than planar. This relates to the ionic radius of the iron, which is in a high-spin Fe(II) state. The iron is too large (radius 2.06Å) to fit in the ring of nitrogens with which it coordinates; it is 0.6Å out of the plane of the ring, which is therefore distorted.


Close-up
and a perpendicular view

Oxyhaemoglobin: the R state

The salt bridges listed for the T in the previous section are broken in the R state. The carboxyl-terminal residues of all the subunits are able to rotate.

In contrast to deoxyhaemoglobin, the haem group is planar and the iron ion lies in the plane of the ring, as it is in a low-spin Fe(II) state with a smaller radius (1.98Å). All six coordination positions of the ion are occupied: the bound oxygen molecule accounts for the sixth.

Examine the structure of oxyhaemoglobin (tetramer provided by Brookhaven).

Close-up

Perpendicular view:

Close-up

Here is Part 3, Allosteric Mechanism


Back to Main PPS Index J. Walshaw