A universal structural deformation in all heme proteins

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Chemists and physicists from Switzerland and Germany have shown that the typical deformation of respiratory heme proteins also occurs in heme proteins not involved in the respiratory function.

Image:A model of heme, which is an organic ring molecule surrounding an atom of iron and is a major component of hemoglobin in red blood cells. The iron atom allows both binding of oxygen and its transport in the blood stream, as well as many other biochemical processes. Credit: iStock photos (user: theasis)

The structure-function relationship is at the heart of biology: specific structural changes in proteins are usually associated with specific functions. This is particularly the case with hemoproteins, which have a wide range of functions, such as oxygen fixation and transport, and neurotransmission.

In humans, the most important protein involved in electron transfer is Cytochrome c, which is involved in cellular respiration in the respiratory chain, transporting one electron per molecule. As such, it is associated with the inner mitochondrial membrane.

Like all heme proteins, the active center of cytochrome c is the so-called "heme porphyrin". The electron transfer properties of cytochrome c have been associated to the "ruffled" deformation of its heme. In contrast, the "domed" deformation of the heme is the hallmark of respiratory proteins such as hemoglobin and myoglobin.

In a new experiment, a team of scientists led by Majed Chergui at EPFL’s School of Basic Sciences, with colleagues at the Paul-Scherrer Institut and the European X-ray Free Electron Laser (Hamburg) have found that Cytochrome c also undergoes doming.

To carry out their study, the researchers used cutting-edge ultrafast X-ray spectroscopic techniques. They activated the heme using ultrashort, energizing laser pulses, and monitored its evolution using another ultrashort X-ray pulse from an X-ray free-electron laser to record X-ray absorption and X-ray emission as a function of time.

X-ray absorption is sensitive to the structure of heme, while X-ray emission offers a fingerprint of its electronic states. By combining the two, the scientists have unambiguously determined that the system undergoes doming and goes back to its initial state via a cascade among spin states.

"The conclusions of our work show that doming is a universal feature of all heme proteins and is not limited to respiratory ones (hemoglobin and myoglobin)," says Majed Chergui. "The question that arises now is the extent to which doming intervenes in the electron transfer function of cytochrome c."

Other contributors

  • Polish Academy of Sciences
  • Adam Mickiewicz University