Ann Taylor/Hemoglobin

Hemoglobin is an oxygen-transport protein. Hemoglobin is an allosteric protein. It is a tetramer composed of two types of subunits designated α and β, with stoichiometry . The of hemoglobin sit roughly at the corners of a tetrahedron, facing each other across a at the center of the molecule. Each of the subunits prosthetic group. The give hemoglobin its red color.

The α and β subunits have very similar structures, despite their sequence differences. We will use a single to examine the subunit structure more closely. The 6 major and 2 short α-helices that make up the structure of a Hb subunit (the "globin fold") are , which is the traditional naming scheme. The helices form an approximately-cylindrical bundle, with the heme and its central Fe atom bound in a (hydrophobic = grey; hydrophilic = purple). The proximal histidine (the tightest protein-Fe intraction) is often called , since it is residue 9 on helix F (it is residue 87 in the human α chain). A second histidine is near the bound oxygen, and is referred to as the . In the deoxy state, the Fe2+ is of the porphyrin ring. When oxygen is bound, the iron changes spin state, resulting in the iron moving of the heme.

Perhaps the most well-known disease caused by a mutation in the hemoglobin protein is sickle-cell anemia. It results from a mutation of the sixth residue in the β hemoglobin monomer from . This hemoglobin variant is termed 'hemoglobin S' (2hbs).

Hemoglobin subunit binding O₂

For hemoglobin to function as an oxygen-carrier in the blood, it must have an equilibrium between the two main states of its quaternary structure, the unliganded "deoxy" or "T state" versus the liganded "oxy" or "R state". The unliganded (deoxy) form is called the "T" (for "tense") state because it contains extra stabilizing interactions between the subunits, specifically . In the high oxygen affinity R-state conformation, these ionic interactions , and the tetramer is described as "relaxed". 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.

The Bohr effect is the increased stability of the T state due to protonation of histidine residues, especially of the beta chains. This is the C terminal residue of the beta chain. In the T state, the C terminal carboxylate group interacts with the positively charged side chain of lysine 40 of an alpha chain. When His 146 is protonated, it can also form an ionic interaction with Asp 94. This second interaction is one of several interactions which stabilizes the T state at lower pH.

Content Donators

Much of this page's content originally came from the Hemoglobin page. To ensure stability during my class and to include some specific data we will be using in a paper discussion, this page was created.