Myoglobin and hemoglobin are oxygen-binding proteins. Hemoglobin is found in blood, and myoglobin is abundant in skeletal and cardiac muscle. Hemoglobin is an oxygen-transporter, and myoglobin is an oxygen-storer.
Myoglobin is a globular protein made up of a single polypeptide chain. Hemoglobin is also a globular protein, but it is a tetramer and is composed of 4 polypeptide chains. It is an α2β2-type tetramer, with two identical α chains and two identical β chains. Each of hemoglobin’s four subunits is very similar to the polypeptide chain making up myoglobin.
The myoglobin polypeptide chain consists of 8 α-helix sections, which are denoted A-H. Each polypeptide chain of the four hemoglobin subunits also consists of these 8 alpha-helix sections. Between these helices are connecting regions named after the helices they connect - e.g. AB region. Amino acids in each helix section are numbered - e.g. His F8.
Both myoglobin and hemoglobin have a prosthetic group. The prosthetic group found in both myoglobin and hemoglobin is the heme group, made up of a protoporphyrin ring and a central iron atom.
There is a heme group in each of hemoglobin’s subunits, as well as in myoglobin’s polypeptide chain, in the cleft between the E and F helices.
Iron can interact with 6 ligands, and four of these are provided by the nitrogen atoms of the pyrroles in the porphyrin ring. A fifth is provided by the imidazole side chain of His F8. When oxygen binds to the iron, that is a 6th ligand! Note that when oxygen is added on, it is tilted at 60° to the perpendicular.
A really cool conformational change happens when oxygen binds to the iron in the heme group. This cool phenomenon is of no consequence in myoglobin, but hemoglobin’s biological function depends on it. Before the binding of oxygen, steric constraints result in the ferrous iron lying 0.055 nm above the porphyrin plane. The binding of oxygen causes the iron to be drawn into the plane of the porphyrin ring, so that it is only 0.026 nm above it. The movement of the iron drags His F8 along with it and sets off a chain of conformational changes in hemoglobin that results in increased affinity of the heme groups of adjacent subunits for oxygen.
In hemoglobin, the four subunits - the two α subunits and the two β subunits - are arranged into two dimeric halves - one α1β1-subunit pair and one α2β2-subunit pair. Each of these dimeric halves moves as one rigid body. Subunits interact mostly with dissimilar chains - in other words, α subunits interact with β subunits, but not α subunits, and β subunits interact with α subunits, but not β subunits. There are two types of contacts between the two dimeric halves of hemoglobin - packing contacts and sliding contacts. Packing contacts do not shift during the conformational changes that occur after the binding of oxygen, while sliding contacts do.
When oxygen binds, the conformational change results in the dimeric halves rotating 15° relative to one another. Hemoglobin’s two conformations are called the T (for tense or taut) and R (for relaxed) forms. When hemoglobin is in the T form, oxygen is only accessible to the heme groups of the α-chains. Steric hinderance prevents it from binding to the chains. This steric hindrance is not present in the R conformational state. Hemoglobin resists oxygenation because its deoxygenated form, the T form, is stabilized by certain hydrogen bonds and interchain salt links. These interactions are broken in the oxygenated form, the R form, where hemoglobin is stabilized in a different conformation.
Meanwhile, myoglobin does not easily release oxygen. When myoglobin binds oxygen, it becomes oxymyoglobin. Oxymyoglobin releases oxygen during times of extreme oxygen deprivation, like when you’re exercising.
While Myoglobin’s O2-binding interaction displays classical Michaelis-Menten-type saturation behaviour, Hemoglobin’s interaction results in a sigmoid-shaped curve rather than a hyperbolic one. The sigmoid shape allows us to draw some conclusions. Binding of oxygen to one subunit of hemoglobin strongly enhances binding of oxygen to other subunits - a phenomenon called cooperativity.
Hemoglobin binds oxygen in the lungs, where the partial pressure of oxygen is around 100 torr. Here, 98% of hemoglobin has oxygen bound to it. In the capillaries of some tissues, the partial pressure of oxygen is 40 torr, and the hemoglobin releases oxygen. Here, 6% of hemoglobin has oxygen bound to it. The 92% difference is thanks to cooperativity. If hemoglobin’s curve was hyperbolic, then only 79% of hemoglobin would have oxygen bound in the lungs, and 28% of hemoglobin would have oxygen bound in the capillaries, for a difference of 51%. So the cooperativity means that hemoglobin is… 92/51% = 1.8 times more efficient at delivering oxygen!
MYOGLOBIN 3D MODELS: 3dprint.nih.gov/discover/3dpx...
3dprint.nih.gov/discover/3dpx...