Question

Describe some of the interactions that stabilize the T and R states of hemoglobin.


(please more than 150 words!! Will rate and thumbs up!!)

Answer 1

SOLUTION:

1)Hemoglobin, its function as an oxygen-carrier in the blood is fundamentally linked to the equilibrium between the two main states of its quaternary structure, the unliganded "deoxy" or "T state" versus the liganded "oxy" or "R state".
2) The unliganded (deoxy) form is called the "T" (for "tense") state because it contains extra stabilizing interactions between the subunits. In the high-affinity R-state conformation the interactions which oppose oxygen binding and stabilize the tetramer are somewhat weaker or "relaxed".
3) In some organisms this difference is so pronounced that their Hb molecules dissociate into dimers in the oxygenated form. Structural changes that occur during this transition can illuminate how such changes result in important functional properties, such as cooperativity of oxygen binding and allosteric control by pH and anions.
4)Hemoglobin is definitely not a pure two-state system, but the T to R transition provides the major, first-level explanation of its function
5)The hemoglobin molecule (or "Hb") is a tetramer of two α and two β chains, of 141 and 146 residues in human. They are different but homologous, with a "globin fold" structure similar to myoglobin.
Here we see a single α chain of hemoglobin, starting with an overview of the subunit.
6) The 6 major and 2 short α-helices that make up the structure of a Hb subunit (the "globin fold") are labeled A through H, which is the traditional naming scheme. For example, the proximal histidine (the tightest protein Fe ligand) is often called His F9, since it is residue 9 on helix F (it is residue 87 in the human α chain). The helices form an approximately-cylindrical bundle, with the heme and its central Fe atom bound in a hydrophobic pocket between the E and F helices.
7)The heme is quite domed in the blue T-state (deoxy) form, with the 5-coordinate, high-spin Fe (yellow ball) out of the plane. In the pink R-state form a CO molecule is bound at the left; the Fe, now 6-coordinate low-spin, has moved into the heme plane, which has flattenened.
8)The proximal His (at right) connects the Fe to helices on the proximal side, making the Fe position sensitive to changes in the globin structure and vice versa. Remember that this scene shows a subunit in the all-unliganded versus the all-liganded states of Hb; when oxygen binds to just one subunit, then its internal structure undergoes some but not all of these changes, depending on conditions.
9)O2 binds in the same place as CO, with similar effects on the structure; however, for O2 the outer atom is angled rather than straight. The equilibrium between free and bound O2 is very rapid, with on and off rates that are sensitive to protein conformation.
10) Both CO and NO dissociate from the Fe atom very slowly, so that these gases act as respiratory poisons. The α and β chains differ somewhat in their rates and relative affinities for O2 and other ligands, by virtue of heme-pocket differences, but the differences between affinities in the R vs T quaternary states are much larger