The scientists behind the new study have visualised the structure of a protein called Microbacterium hydantoin permease, or 'Mhp1', which lives in the oily membrane that surrounds bacteria cells. It belongs to a group of proteins known as 'transporters' which help cells take up certain substances from the environment around them.
This is the first time scientists have been able to show how a transporter protein opens and closes to allow molecules across the membrane and into the cell, by accurate analysis of its molecular structure in different states.
Professor So Iwata from Imperial College London's Division of Molecular Biosciences in the Department of Life Sciences, one of the authors of the new study, explains that solving the structure of the Mhp1 bacterial transporter protein is very important because hundreds of similar transporters are found in the membranes of human cells:
"Transporter proteins play an important role in the human body - they are responsible for letting different substances, including salts, sugars and amino acids, into our cells and are targets for a large number of drugs. Understanding the details of how this transport mechanism works may help researchers to design new, more effective, drugs in the future," he said.
The group's research into this protein began in 2000 with a joint project with the Ajinomoto Company from Japan. This company work with a bacterium called Microbacterium liquefaciens which has the Mhp1 protein in its cell membranes. The project revealed that Mhp1 helps the uptake of amino acid-like molecules called hydantoins across the otherwise impermeable cell membrane.
Professor Peter Henderson from the University of Leeds, co-author of the study, said: "The major problem was to produce enough protein for the structural studies. We developed methods for the amplified expression of the Mhp1 protein in a genetically-engineered host organism, Escherichia coli, and procedures for the subsequent efficient purification of the protein from the cell membranes. We could then maintain a 'pipeline' to supply an exceptional amount of the membranes containing the excess Mhp1 protein to our colleagues at Imperial".
Professor Iwata and his colleagues analysed the structure of Mhp1 using the facilities at the Membrane Protein Laboratory (MPL), which is an Imperial College outstation at the Diamond Light Source national synchrotron facility in Oxfordshire. They used the MPL, which is a dedicated facility for membrane protein structural studies, to build an accurate picture of the Mhp1 protein binding to hydantoin.
The researchers analysed the structure of Mhp1 before and after it had taken in a hydantoin molecule from outside the cell, and also used the structure of a related transporter, vSGLT, for insight into the latter stages of the take-up process. These three structures revealed new molecular-level detail of how Mhp1 transports a hydantoin molecule across the cell membrane.
The researchers saw that the Mhp1 protein opens up on its outer-facing side, allowing the hydantoin molecule to move inside. Once the hydantoin is bound, the 'door' to the outside world closes behind it, ensuring that no other substances have been let in. Then the gate on the inward-facing side opens to release the hydantoin into the cell.
Professor Iwata comments on the significance of the discovery, saying: "Our research has revealed the detailed molecular function of an important membrane protein. We now know how the protein facilitates the movement hydantoin across the cell membrane without letting any other substances through at the same time. This mechanism is likely to be shared by many cell membrane proteins, including those in the human body, so this is an important step forward in our understanding of the fundamental processes which occur in our cells."
Professor Iwata leads an international team of scientists at the Membrane Protein Laboratory at the Diamond Light Source. The MPL is a joint venture between Imperial College London and Diamond Light Source, with funding from the Wellcome Trust and the Japan Science and Technology Agency.
Professor Henderson is Scientific Director of the EU-funded European Membrane Protein consortium, 'EMeP', which promotes collaborative research on membrane proteins between 18 European Institutions.
The Science Express research out today was carried out by researchers from Imperial College and the University of Leeds, in collaboration with scientists from Japan and Iran. The work was funded in the UK by the BBSRC, the Japan Science and Technology Agency, the EU, the Wellcome Trust and Ajinomoto Co.
Danielle Reeves | alfa
Atomic-level motion may drive bacteria's ability to evade immune system defenses
24.04.2017 | Indiana University
Two-dimensional melting of hard spheres experimentally unravelled after 60 years
24.04.2017 | University of Oxford
More and more automobile companies are focusing on body parts made of carbon fiber reinforced plastics (CFRP). However, manufacturing and repair costs must be further reduced in order to make CFRP more economical in use. Together with the Volkswagen AG and five other partners in the project HolQueSt 3D, the Laser Zentrum Hannover e.V. (LZH) has developed laser processes for the automatic trimming, drilling and repair of three-dimensional components.
Automated manufacturing processes are the basis for ultimately establishing the series production of CFRP components. In the project HolQueSt 3D, the LZH has...
Reflecting the structure of composites found in nature and the ancient world, researchers at the University of Illinois at Urbana-Champaign have synthesized thin carbon nanotube (CNT) textiles that exhibit both high electrical conductivity and a level of toughness that is about fifty times higher than copper films, currently used in electronics.
"The structural robustness of thin metal films has significant importance for the reliable operation of smart skin and flexible electronics including...
The nearby, giant radio galaxy M87 hosts a supermassive black hole (BH) and is well-known for its bright jet dominating the spectrum over ten orders of magnitude in frequency. Due to its proximity, jet prominence, and the large black hole mass, M87 is the best laboratory for investigating the formation, acceleration, and collimation of relativistic jets. A research team led by Silke Britzen from the Max Planck Institute for Radio Astronomy in Bonn, Germany, has found strong indication for turbulent processes connecting the accretion disk and the jet of that galaxy providing insights into the longstanding problem of the origin of astrophysical jets.
Supermassive black holes form some of the most enigmatic phenomena in astrophysics. Their enormous energy output is supposed to be generated by the...
The probability to find a certain number of photons inside a laser pulse usually corresponds to a classical distribution of independent events, the so-called...
Microprocessors based on atomically thin materials hold the promise of the evolution of traditional processors as well as new applications in the field of flexible electronics. Now, a TU Wien research team led by Thomas Müller has made a breakthrough in this field as part of an ongoing research project.
Two-dimensional materials, or 2D materials for short, are extremely versatile, although – or often more precisely because – they are made up of just one or a...
20.04.2017 | Event News
18.04.2017 | Event News
03.04.2017 | Event News
24.04.2017 | Physics and Astronomy
24.04.2017 | Materials Sciences
24.04.2017 | Life Sciences