Seeing where the protons are

Many fundamental processes in biology such as signalling and energy conversion make use of the transport and storage of protons within proteins. One widely studied example occurs in vision; in the membrane protein bacteriorhodopsin. Absorption of a photon leads to isomerisation of the retinal molecule which eventually leads to transport of a protein across the cell membrane, resulting in an electrical signal in your nerves.

Hence, a key question concerns the location of the protons at different stages of the process. Generally, high-resolution crystal structures (from X-rays) do not reveal the location of protons.

Over the past decade it has become more appreciated that the location of water molecules inside the protein can provide a key functional role due to their ability to form hydrogen bonds which allow take up and release of protons.

In 2006 a Nature paper by Garczarek and Gerwert used infra-red spectroscopy to investigate the proton dynamics and argued that the water molecules inside the protein were responsible for storing the protons. This picture was supported by a PNAS paper by Mathias and Marx, reporting quantum dynamical calculations which treated the protons at the fully quantum level. 

However, a PNAS paper from two years ago [featured in a post two days ago] offers a distinctly different picture. It argues that the proton is shared between oxygen atoms at the carboxylic acid end of the amino acids Glu194 and Glu204.

 Glu=glutamine

The carboxylic acid is the C-OOH group at the lower right

So what do I learn from all this?

• there are still fundamental problems in molecular biology which are still waiting to be solved [and some of them involve quantum dynamics!]
• one needs to be very careful in the interpretation of experiments and calculations. This is why the method of multiple hypotheses are so important.
• the character of hydrogen bonds is somewhat universal and so deducing from spectroscopic signatures which molecules the O-...H...-O unit is attached to is a tenuous process.
• as emphasized in the earlier post, small details in the crystal structure can have significant implications.