Haemoglobin

Family Ties

Haemoglobin is part of the large globin family of haem-containing proteins that are involved in the binding and/or transport of oxygen. These proteins are widely distributed in many organisms. Examples of some other globin proteins found in this family are:

Ø Myoglobin (used as a reserve supply of oxygen, and facilitates the movement of oxygen within muscles)

Ø Neuroglobin (involved in oxygen transport in the brain)

Ø Cytoglobin (involved in intracellular oxygen storage or transfer)

Ø Leghaemoglobin (provides oxygen to bacteroids, which is essential for symbiotic nitrogen fixation)

Ø Erythrocruorin (giant haemoglobin of worms)

Ø Plant haemoglobin (may act as an oxygen sensor)

Ø Flavohaemoglobin (involved in NO detoxification)

All of these proteins share a common alpha-helical globin structure.

What InterPro Tells Us

As the same signatures hit many of the globins, only the beta globin chain will be used as an example:

P68871 Human Beta Globin Chain

InterPro Domain Architecture

InterPro Entry	Method Accession	Graphical Match	Method Name
IPR000971	PF00042		globin
IPR000971	PS01033		GLOBIN
IPR002337	PR00814		BETAHAEM
IPR009050	SSF46458		Globin_like
IPR012292	G3D.1.10.490.10		Globin_related
Classification	PDB Chain/Domain ID	PDB Chain/Structural Domains
1ird	1irdB
1.10.490.10.4	1irdB0
a.1.1.2	d1irdb_

From the graphical match above, you can see that the signatures (method accession) are grouped into four InterPro entries for the human alpha globin chain. These reflect hierarchical relationships between the different signatures. IPR009050, the globin-like family, is top of the hierarchy and has one signature, SSF46458 from the SUPERFMAILY database. This entry represents any protein with a globin-like structure that is evolutionarily related to globin, which includes the entire globin family, as well as truncated haemoglobins and phycocyanin-like phycobilisome proteins. The entry IPR012292, the globin-related family, represents proteins more closely related in sequence and structure than those found in IPR009050 (lacks the more distantly related phycocyanin-like phycobilisome proteins), and has one signature: G3D.1.10.490.10 from the Gene3D database. The next entry is IPR000971, the globin family, that represents the globin family itself (closely related in sequence), and has two signatures: PF00042 from the PFAM database and PS01033 from the PROSITE database. The remaining entry, IPR002337, the beta-haemoglobin family, is the most specific classification, and is represented by one signature: PR00814 from the PRINTS database. As all five of these signatures cover the same sequence, they are related to one another: IPR009050 is the parent of IPR012292, which in turn is the parent of IPR000971, which is itself the parent of IPR002337:

The remaining three entries in the table above are from the structural database PDB (green stripe), and from the structural classification databases CATH (pink stripe) and SCOP (black stripe) (the names such as d1irdb_ being derived from the PDB entry upon which it is based, here PDB entry 1ird, chain B). The graphical match for the PDB entry 1ird displays the length of the original PDB entry, which covers the entire protein. The CATH (1irdB0) and SCOP (d1irdb_ ) databases give information on the classification of this protein.

What the Structure Tells Us

Haemoglobin was the first protein to have its 3-dimensional structure determined by Max Perutz and his colleagues at Cambridge University in the 1950s, and has served as a model to correlate a protein’s structure with its function. The structures of the different globin chains can be viewed through InterPro using AstexViewer®, which is linked from the InterPro Match Table of each protein via the logo (please note, there is no link directly from this page to the AstexViewer® for the protein discussed above, therefore you need to go to the link on the InterPro pages for P68871). The AstexViewer® displays the PDB structure with the particular CATH or SCOP domain highlighted in yellow. There are several structures associated the different haemoglobin chains in the Protein Data Bank (PDB). A detailed description and visualisation of the structural features of haemoglobin can be found at the PDB ‘Molecule of the Month’, providing insights into the molecular basis of action for this oxygen carrier.

Next: Table of Haemoglobin and Related Proteins

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