Nav: Home

Tuberculosis bacterium uses sluice to import vitamins

March 25, 2020

A transport protein that is used by the human pathogen Mycobacterium tuberculosis to import vitamin B12 turns out to be very different from other transport proteins. It contains a huge water-filled cavity, in which hydrophilic substances are transported across the cell membrane. This discovery, which changes our understanding of bacterial physiology, was made by imaging the transport protein using cryo-electron microscopy. The results were published in the journal Nature on 26 March.

The tuberculosis bacterium has all the genes required to produce vitamin B12 but, for some reason, it still needs to import this vitamin for successful cell division. To do so, it uses a transport protein that is part of a large family of ATP-binding cassette (ABC) transporters. Interestingly, the vitamin B12 transporter is also implicated in the transport of antimicrobial peptides such as bleomycin. 'And it is very odd to have a single transporter for two very different types of molecules,' says Professor of Biochemistry Dirk Slotboom.

Cavity

Slotboom and his team, together with their colleague Albert Guskov, set out to elucidate the protein structure of the enigmatic transporter. 'This was a long process but we finally cracked it using cryo-electron microscopy,' says Slotboom. This was performed at the SLAC National Accelerator Laboratory, Menlo Park, CA, USA. The structure revealed a major surprise: a water-filled cavity that spans the entire cell membrane, measuring a massive 7,700 cubic Angstrom. 'That is as big as seven vitamin B12 molecules.'

This cavity appears to simply transport water together with any substances that might be in it. 'You could compare it with a sluice,' explains Slotboom. 'You let the water in and everything that is in it.' It does explain why the transporter can handle both antibiotic peptides and vitamin B12. Since it is non-selective, it must be an inefficient transport system. This does not matter for the uptake of vitamin B12 by Mycobacterium tuberculosis, as the cells only need to take up very few of these molecules during their reproductive cycle, which lasts around 24 hours.

Antibiotics

The non-selective transport system is totally different from known transporters. 'As such, it changes the way that we look at the physiology of bacteria. There are strong indications that other bacterial species have a similar system, which means that they pick up random molecules from their environment.' It also offers an interesting perspective on the treatment of tuberculosis: 'If we could stimulate the activity of this transporter, it might import antibiotics more efficiently, making it easier to kill these cells. We realize, though, that this may not be straightforward, as the bacterium uses effective strategies to keep antibiotics out.'

The next step is to find out how the transporter works. 'We expect that inside the cell, the sluice is emptied by binding and hydrolysing ATP. But we do not know how it opens on the outside, to let new molecules in.' The transport protein is a dimer and the two halves appear to protrude on the outside - where they may somehow open up to let fresh cargo in. 'Maybe we can find a way to loosen this cap and let more antibiotics in.'

Human cells

There is also a distinct possibility that a similar sluice-type transporter is present in human cells, says Slotboom. In our intestines, vitamin B12 is first bound to a peptide called intrinsic factor and then taken up by epithelial cells. 'It ends up in lysosomes, vesicles full of enzymes, where the intrinsic factor is degraded. Next, the vitamin B12 is released from the lysosome into the cells. I strongly suspect that this involves a similar non-specific transporter.'
-end-
Simple science summary

Scientists from the University of Groningen discovered that the bacterium that causes tuberculosis uses a strange protein to import vitamin B12. Transport proteins that import substances from the environment are usually selective. But, in addition to vitamin B12, this particular transporter can import very different molecules, including the antibiotic peptide bleomycin. The mystery was solved by analysing the structure of the transport protein using an electron microscope. It turned out that the protein has a large water-filled cavity that spans the entire thickness of the cell membrane, taking anything in the water with it. It is the first time that such a novel, non-selective transport mechanism has been observed. However, the scientists believe that it may be common in bacteria and possibly also in human cells.

Reference: S. Rempel, C. Gati, M. Nijland, C. Thangaratnarajah, A. Karyolaimos, J. W. de Gier, A. Guskov & D. J. Slotboom: A mycobacterial ABC transporter mediates the uptake of hydrophilic compounds. Nature, 26 March 2020

University of Groningen

Related Cell Membrane Articles:

Using light's properties to indirectly see inside a cell membrane
Using properties of light from fluorescent probes is at the heart of a new imaging technique developed at Washington University's McKelvey School of Engineering that allows for an unprecedented look inside cell membranes.
Cell 'membrane on a chip' could speed up screening of drug candidates for COVID-19
Researchers have developed a human cell 'membrane on a chip' that allows continuous monitoring of how drugs and infectious agents interact with our cells, and may soon be used to test potential drug candidates for COVID-19.
Scientists synthesize novel artificial molecules that mimic a cell membrane protein
Scientists at Tokyo Institute of Technology (Tokyo Tech) recently developed an artificial transmembrane ligand-gated channel that can mimic the biological structure and function of its natural counterpart.
Across the cell membrane
Aquaporins and glucose transporters facilitate the movement of substances across biological membranes and are present in all kingdoms of life.
Location, location, location: The cell membrane facilitates RAS protein interactions
Many cancer medications fail to effectively target the most commonly mutated cancer genes in humans, called RAS.
New self-forming membrane to protect our environment
A new class of self-forming membrane has been developed by researchers from Newcastle University, UK.
Cell membrane proteins imaged in 3D
A team of scientists including researchers at the National Synchrotron Light Source II have demonstrated a new technique for imaging proteins in 3D with nanoscale resolution.
Researchers refute fifty-year old doctrine on cell membrane regulation
The cell membrane can be regarded as the boundary between life and non-life.
Proof of sandwiched graphene-membrane superstructure opens up a membrane-specific drug delivery mode
Researchers from the Institute of Process Engineering (IPE) of the Chinese Academy of Sciences and Tsinghua University (THU) proved a sandwiched superstructure for graphene oxide (GO) that transport inside cell membranes for the first time.
Membrane madness: The ins and outs of moving materials through the cell
The cell membrane is a fatty layer that forms a border between the inside of the cell, its various structures and the outside world.
More Cell Membrane News and Cell Membrane Current Events

Trending Science News

Current Coronavirus (COVID-19) News

Top Science Podcasts

We have hand picked the top science podcasts of 2020.
Now Playing: TED Radio Hour

Debbie Millman: Designing Our Lives
From prehistoric cave art to today's social media feeds, to design is to be human. This hour, designer Debbie Millman guides us through a world made and remade–and helps us design our own paths.
Now Playing: Science for the People

#574 State of the Heart
This week we focus on heart disease, heart failure, what blood pressure is and why it's bad when it's high. Host Rachelle Saunders talks with physician, clinical researcher, and writer Haider Warraich about his book "State of the Heart: Exploring the History, Science, and Future of Cardiac Disease" and the ails of our hearts.
Now Playing: Radiolab

Insomnia Line
Coronasomnia is a not-so-surprising side-effect of the global pandemic. More and more of us are having trouble falling asleep. We wanted to find a way to get inside that nighttime world, to see why people are awake and what they are thinking about. So what'd Radiolab decide to do?  Open up the phone lines and talk to you. We created an insomnia hotline and on this week's experimental episode, we stayed up all night, taking hundreds of calls, spilling secrets, and at long last, watching the sunrise peek through.   This episode was produced by Lulu Miller with Rachael Cusick, Tracie Hunte, Tobin Low, Sarah Qari, Molly Webster, Pat Walters, Shima Oliaee, and Jonny Moens. Want more Radiolab in your life? Sign up for our newsletter! We share our latest favorites: articles, tv shows, funny Youtube videos, chocolate chip cookie recipes, and more. Support Radiolab by becoming a member today at Radiolab.org/donate.