Question

Describe the T and R conformaions of hemoglobin with regards to: oxygen binding affinity; change in heme conformation upon binding to oxygen; effect that a conformational change in a single subunit has on other subunits (ex: cooperativitt)

Answer 1

Hemoglobin is an oxygen binding protein found in erythrocytes which transports oxygen from lungs to tissues. It belongs to a family of hem-proteins which contain a heme prosthetic group. Single hemoglobin molecule is a tetramer made of four polypeptide globin chains and each globin subunit contains a heme moiety formed of an organic protoporphyrin ring and a central iron ion available in ferrous state (Fe²⁺).

Max Perutz in 1959 solved the three-dimensional structure of hemoglobin using X-ray crystallography.

T and R Conformations of Hemoglobin

Hemoglobin molecule exists in two distinct conformational states:

1. T-state also called tense state

2. R-state also called relaxed state.

The T state has a less of an affinity for oxygen than the R state.

Lets see about T conformation of hemoglobin

It is one of the two quaternary forms of hemoglobin that predominates in absence of oxygen.The T-state is the deoxy form of hemoglobin which means that it lacks an oxygen species and is also known as "deoxyhemoglobin”.

Oxygen binding affinity: Has less of an affinity for oxygen than the R state. Haemoglobin in the T-state has a higher affinity for hydrogen ions than for oxygen. As the pH goes down (so H⁺ goes up), hemoglobin enters the T state and its affinity for oxygen goes down.

Change in heme conformation upon binding to oxygen: T state hemoglobin (deoxy hemoglobin) undergoes several conformational changes upon binding with oxygen.

In T state of hemoglobin, the iron ion is bound to the lone pair of nitrogen contained in Histidine side chain. This bond pulls iron out of the porphyrine plans. When oxygen binds to the iron ion, then new bond pulls back iron on the heme plan. As soon as the iron cation within hemoglobin begins to move, the Histidine residue and the alpha helix of hemoglobin also start moving. As a result, the carboxyl terminal end of the alpha-helix, which resides at the interface between the two alpha- and beta-dimers also moves. The positional changes of the carboxyl terminal end create favorable conditions for transitions between the T- and the R-states of hemoglobin.

Effect that a conformational change in a single subunit has on other subunits: The positional changes of the carboxyl terminal end create favorable conditions for transitions between the T- and the R-states of hemoglobin. When one strand of hemoglobin binds oxygen, the hemoglobin rearranges in a manner that favors additional oxygen binding. When the next oxygen is bound, another conformational change occurs to further supplement binding; Thus, hemoglobin can sequentially increase its affinity for oxygen as more and more of its strands bind oxygen.

Lets see about R Conformation of Hemoglobin

The R-state is the fully oxygenated form also called oxyhemoglobin.

Oxygen binding affinity: Has more of an affinity for oxygen than the T state.

Change in heme conformation upon binding to oxygen: When hemoglobin is oxygenated (right), the heme group adopts a planar configuration. The conformational change in the heme group causes the protein to change its conformation.

Effect that a conformational change in a single subunit has on other subunits: In the high-affinity R-state conformation the interactions which oppose oxygen binding and stabilize the tetramer are somewhat relaxed.

Summary:The hemoglobin exists in T and R states and each state has different affinities for oxygen. The binding of oxygen to each state of hemoglobin result in conformational changes.