Gate Like Protein Complexes In The Cell Membranes

Almost all living organisms from bacteria to humans have gate-like protein complexes in their cell membranes that get rid of unwanted or life-threatening molecules. This is not always to human advantage, since in the case of bacteria or cancer cells these complexes, knowing as ABC transporters, are also responsible for resistance to antibiotics or chemotherapy.

The study investing considerable effort in preparing samples of sensitive membrane protein complexes; in such a way that they can be examining in membrane environment by means of cryo-electron microscopy. Cryo-electron microscopy delivers high-resolution images by freezing the molecules so that blurring is reducing to a minimum when they are in motion.

Gate like protein complexes

Complex molecules, such as ABC transporters, but also to observe them at work, snapshots of different stages are required; by trigger these stages deliberately by supplying the transporter with different concentrations of ATP and ADP. Without the energy supply of ATP, the transporter is unable to translocate molecules against the concentration gradient between the cell interior and its surroundings.

The study showing high-resolution conformations of an ABC export complex composing of two different protein subunits. The researchers were also able to make intermediate stages of the transport process visible for the first time. Since it was possible to display all the motions of a cellular machine in almost atomic resolutio.

Mechanism of ABC transporters

The transport mechanism of ABC transporters; which were previously the subject of controversial debate and are highly relevant for medicine. In addition, the researchers were able to observe for the first time how the gates open inwards or outwards; The resolution of 2.8 Angstrom is the highest resolution ever achieving in the imaging of an ABC transporter structure; with the help of cryo-electron microscopy.

However, the study reveal that phosphate release, not ATP hydrolysis, triggers the return of the exporter to the IF conformation. By mapping the conformational landscape during active turnover; aided by mutational and chemical modulation of kinetic rates to trap the key intermediates; study resolving fundamental steps of the substrate translocation cycle of asymmetric ABC transporters.