Nav: Home

Structure of protein nano turbine revealed

August 22, 2019

Cells rely on protein complexes known as ATP synthases or ATPases for their energy needs - adenosine triphosphate (ATP) molecules power most of the processes sustaining life. Structural biologist Professor Leonid Sazanov and his research group from the Institute of Science and Technology Austria (IST Austria) in Klosterneuburg, Austria have now determined the first atomic structure of the representative of the V/A-ATPase family, filling in the gap in the evolutionary tree of these essential molecular machines. These results obtained using the latest cryo-electron microscopy methods revealed a turbine or water mill similar structure of the enzyme and have now been published in the journal Science.

Rotary power

ATP synthases/ATPases are large membrane protein complexes which share overall gross building plans and rotary catalysis mechanisms. This protein family includes F-type enzyme found in mitochondria (power factories of the cell), chloroplasts (organelles that conduct photosynthesis in plants) and bacteria; V (vacuolar)-type found in intracellular compartments in eukaryotes (higher organisms with a nucleus) and A (archaeal)-type found in prokaryotes - archaea (ancient microorganisms) and some bacteria.

Different flavors of ATPases


F- and A-type enzymes usually function to produce ATP, driven by proton flow across the membrane. V-type enzymes usually work in reverse, using ATP to pump protons. V- and A-ATPases are similar structurally but they differ from the F-type by having two or three peripheral stalks and additional connecting protein subunits between V1 and Vo. V-type enzymes probably evolved from the A-type and because of these similarities A-type is also termed V/A-ATPase. Some bacteria, including Thermus thermophilus, acquired an A-type enzyme. Long Zhou, postdoc in the Sazanov research group of IST Austria, has purified and studied this enzyme (ThV1Vo) by cryo-EM. In contrast to F-type, for V-type ATPases only the structures of the isolated V1 and Vo domains were determined previously. How V1 is coupled to Vo was therefore not known, and the knowledge about the full catalytic cycle was lacking.

Plasticity and competition

The scientists determined not one, but in total five structures of the entire ThV1Vo enzyme, using cryo-electron microscopy methods developed recently in the so-called "resolution revolution" of this technique. The structures represent several conformational states of the enzyme differing by the position of the rotor inside the stator. Global conformational plasticity of ThV1Vo is revealed as substantial V1 wobbling in space in transition from one state to another. It is a result of mechanical competition between rotation of the bent central rotor and stiffness of the stator. V1-Vo coupling is achieved via close structural and electrostatic match between the shaft and V-type specific subunit linking it to the c-ring. The visualization of the proton path revealed significant differences in the distribution of charged protein residues from that in F-ATPases, with a stricter "check-point" preventing "slipping" of the enzyme.

Why additional complexity?

Instead of a single peripheral stalk of F-type enzymes, A-types such as ThV1Vo have two peripheral stalks, while eukaryotic V-types have three. But what is the advantage of the additional complexity in the already very large protein assembly, along with additional subunits linking V1 and Vo? The F1/V1 domain has a three-fold symmetry and so one ATP molecule is produced (or consumed) per each 120° rotation of the stator inside F1/V1. Professor Leonid Sazanov says: "In V/A-ATPases this step is a one-off 120° rotation, in contrast to F-ATP synthase where it is divided into several sub-steps. Thus, greater plasticity may be required in ThV1Vo in order to link these 120° steps in V1 to smaller per c subunit steps in the Vo c12-ring. This additional flexibility may be afforded in V-types by the additional peripheral stalks and connecting subunits. Our new structures show how this is achieved, providing a framework for the entire V-ATPase family".
-end-


Institute of Science and Technology Austria

Related Science Articles:

75 science societies urge the education department to base Title IX sexual harassment regulations on evidence and science
The American Educational Research Association (AERA) and the American Association for the Advancement of Science (AAAS) today led 75 scientific societies in submitting comments on the US Department of Education's proposed changes to Title IX regulations.
Science/Science Careers' survey ranks top biotech, biopharma, and pharma employers
The Science and Science Careers' 2018 annual Top Employers Survey polled employees in the biotechnology, biopharmaceutical, pharmaceutical, and related industries to determine the 20 best employers in these industries as well as their driving characteristics.
Science in the palm of your hand: How citizen science transforms passive learners
Citizen science projects can engage even children who previously were not interested in science.
Applied science may yield more translational research publications than basic science
While translational research can happen at any stage of the research process, a recent investigation of behavioral and social science research awards granted by the NIH between 2008 and 2014 revealed that applied science yielded a higher volume of translational research publications than basic science, according to a study published May 9, 2018 in the open-access journal PLOS ONE by Xueying Han from the Science and Technology Policy Institute, USA, and colleagues.
Prominent academics, including Salk's Thomas Albright, call for more science in forensic science
Six scientists who recently served on the National Commission on Forensic Science are calling on the scientific community at large to advocate for increased research and financial support of forensic science as well as the introduction of empirical testing requirements to ensure the validity of outcomes.
World Science Forum 2017 Jordan issues Science for Peace Declaration
On behalf of the coordinating organizations responsible for delivering the World Science Forum Jordan, the concluding Science for Peace Declaration issued at the Dead Sea represents a global call for action to science and society to build a future that promises greater equality, security and opportunity for all, and in which science plays an increasingly prominent role as an enabler of fair and sustainable development.
PETA science group promotes animal-free science at society of toxicology conference
The PETA International Science Consortium Ltd. is presenting two posters on animal-free methods for testing inhalation toxicity at the 56th annual Society of Toxicology (SOT) meeting March 12 to 16, 2017, in Baltimore, Maryland.
Citizen Science in the Digital Age: Rhetoric, Science and Public Engagement
James Wynn's timely investigation highlights scientific studies grounded in publicly gathered data and probes the rhetoric these studies employ.
Science/Science Careers' survey ranks top biotech, pharma, and biopharma employers
The Science and Science Careers' 2016 annual Top Employers Survey polled employees in the biotechnology, biopharmaceutical, pharmaceutical, and related industries to determine the 20 best employers in these industries as well as their driving characteristics.
Three natural science professors win TJ Park Science Fellowship
Professor Jung-Min Kee (Department of Chemistry, UNIST), Professor Kyudong Choi (Department of Mathematical Sciences, UNIST), and Professor Kwanpyo Kim (Department of Physics, UNIST) are the recipients of the Cheong-Am (TJ Park) Science Fellowship of the year 2016.
More Science News and Science 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.