Our cells use proteins to carry out many critical cellular functions and are required for life. They function as messengers that send or receive signals and catalysts for chemical reactions, for example. Dysfunctional proteins can cause disease, whether it’s an error in an individual protein or a broader problem with signaling between proteins. Scientists at the University of Göttingen have now learned more about the basis of protein signaling on an atomic level.
Reporting in Nature, researchers led by Professors Kai Tittmann and Ricardo Mata created ultra-high-resolution protein crystals of a human protein. This can reveal the positions of the atoms within the protein by exposing the crystals to a particle accelerator. Using the DESY particle accelerator, the researchers observed positively-charged subatomic particles called protons moving in and around the protein. Parts of the protein that were physically far apart could thus signal to one another instantaneously.
"The proton movements we observed closely resemble the toy known as a Newton's cradle, in which the energy is instantly transported along a chain of suspended metal balls. In proteins, these mobile protons can immediately connect other parts of the protein," explained Tittmann, who is also a Max Planck Fellow at the Max Planck Institute for Biophysical Chemistry in Göttingen.
The research team also generated high-resolution structural data for some other proteins, which showed how two heavy atoms share a proton in a type of bond called low-barrier hydrogen bonding. This resolved an old scientific controversy; we now know that this type of hydrogen bond exists in proteins and is essential to their function.
Quantum chemical calculations helped to model the process and generate a new mechanism for proton communication in proteins. "We have known for quite some time that protons can move in a concerted fashion, like in water for example. Now it seems that proteins have evolved in such a way that they can actually use these protons for signaling."
The researchers suggested that this work can help advance our understanding of protein signaling and how it goes wrong in disease. That may help the development of new therapeutics like adaptable proteins that can be used in a variety of applications, which are more environmentally friendly.
Learn more about the DESY particle accelerator from the video above, and X-ray crystallography from the video below.