Hemoglobin: Introduction to Protein Structure

Hemoglobin is the oxygen-carrying protin in red blood cells. It consists of a polypeptide chain that holds a number of "heme" units: macrocyclic organic molecules that serve as a ligand for iron. The iron reversibly binds to O₂. It also (as we shall see) binds to other molecules; the binding to CO is strong enough to interfere with O₂ transport and leads to CO poisoning.

Primary structure

The "primary structure" is the sequence of amino acid residues. For this protein, this is:

                VAL LEU SER PRO ALA ASP LYS THR ASN VAL LYS ALA ALA          
		TRP 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 ASN 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                  
		VAL HIS LEU THR PRO GLU GLU LYS SER ALA VAL THR ALA          
		LEU TRP GLY LYS VAL ASN VAL ASP GLU VAL GLY GLY GLU          
		ALA LEU GLY ARG LEU LEU VAL VAL TYR PRO TRP 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 ASN ALA LEU ALA HIS          
		LYS TYR HIS                                                  
		VAL LEU SER PRO ALA ASP LYS THR ASN VAL LYS ALA ALA          
		TRP 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 ASN 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                  
		VAL HIS LEU THR PRO GLU GLU LYS SER ALA VAL THR ALA          
		LEU TRP GLY LYS VAL ASN VAL ASP GLU VAL GLY GLY GLU          
		ALA LEU GLY ARG LEU LEU VAL VAL TYR PRO TRP 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 ASN ALA LEU ALA HIS          
		LYS TYR HIS

Convention has this run from the N-terminus to the C-terminus.

Secondary Structure

Most of the chains in hemoglobin exist as part of an α-helix. In any of the Jmol structures below, right-click, select "Select", check "Show Selected Only", then go back and select "Protein" and "Backbone." This will show the orientation of the amide links without the clutter of the side chains. You will see that almost every amide C=O bond is pointed toward a nitrogen that is about 3-4 residues away.

Another common motif is a planar "β-sheet". Here, strands of peptide chains line up side-to-side; again this is a hydrogen-bond donation from an amide N-H to the C=O oxygen.

Tertiary/Quaternary Structure

The tertiary structure is the folding of the chain after formation of helices and sheets. Often, more than one chain is present; in hemoglobin there are actually 4, and the organization as those come together is called the quaternary structure. The chains may be identical or different.

Load molecule:
Deoxyhemoglobin
Oxyhemoglobin
Carboxyhemoglobin

All molecules:
Show the heme units these bind O₂)
Zoom in on heme
Oxyhemoglobin:
Show the bound oxygen units these bind O₂)
Zoom in on heme
Carboxyhemoglobin:
Show the bound carbon monoxide units
Zoom in on heme
Because the heme binds CO more tightly than O₂, CO is poisonous.