Basics of Sickle Cell Who suffers from it? What is Hemoglobin? Fiber formation Protein


Hemoglobin is the oxygen carrier protein in red blood cells.  It is also the protein, which gives red blood cells their red color.  Hemoglobin consists of four subunits, two a and two b; each a and b subunit (refer to image) forms a dimer.  Often, hemoglobin is referred to as a 'dimer of ab dimers.'  The a and b subunits are only slightly different from each other with the main difference arising from the length of the polypeptide chains; the b chain is 5 amino acid residues longer than the a chain.  There are also some differences in the composition of the amino acid residues. 


This figure depicts the b subunit of hemoglobin, which consists of 8  a-helices, labelled A-H.  Each a-helix is shown in a different color.  The protein chain begins with the A-helix (blue) and ends with the H-helix (lavender).  The heme group is shown in red and the bound oxygen is shown in light blue. 


The figure at left shows the heme group, which contains an Iron (Fe) atom at the center (orange).  In the oxy state, oxygen binds to the Fe in the heme group.   


Each hemoglobin subunit contains a heme group.  The heme group is the site of oxygen (O2) binding.  When all four heme moieties bind O2, the structure of hemoglobin changes.  This structural change involves a rearrangement of the ab dimers with respect to each other, where one ab dimer rotates approximately 18° and translates 1 Å with respect to the other dimer.  

1Angstrom (Å) = 10-10m = 3.937 x 10-9 inches


Fig 3.3 Graphic of T-R transition of HbS

When the protein is in the structure that binds O2, the R-state, it binds O2 readily and when it is in the structure that has no O2 bound, the deoxy or T-state(Fig 3.3 and Fig 3.4), it doesn’t bind O2 very well.  This difference in the ability to bind O2 depending on its structural state is what allows hemoglobin to be so efficient in delivering O2 to the tissues.  Once it delivers O2, the structural state changes and it will not bind the delivered O2.  When the Red Blood Cells (RBCs) return to the lungs, the O2 concentration is higher and hemoglobin binds O2 again and changes its structural state.  Understanding how this structural change is effected is a central question in current hemoglobin research. 


Fig 3.4  Relative Motion of Dimers 
This animated figure illustrates the motion of the
a2b2 dimer (thick coils towards front) relative to the a1b1 dimer (thin coils towards rear) in the oxy-to-deoxy transition. Here, the coordinates of oxy- and deoxy-Hb have been superimposed at the a1b1 interface so that the a1b1 dimer remains stationary. The a2b2 dimer rotates by 15 degrees about an axis passing through the a subunits.

image from Jonathan Lukin, Dept. of Biological Sciences, Carnegie Mellon University http://www.andrew.cmu.edu/user/jl2p/Hb_html/gallery.html

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