Researchers from the University's Astbury Centre for Structural Molecular Biology and from the University of Tokyo have for the first time identified key elements of dynein's structure, and the winch-like mechanism by which it moves.
The research – funded by the Biotechnology and Biological Sciences Research Council and the Wellcome Trust – is published in the latest issue of Cell.
Dynein is the largest, but least understood of the three families of motor proteins, yet it is responsible for many key processes, such as powering the movement of sperm and eggs, and helping cells divide. It is also responsible for transporting molecular cargo within cells such as motor neurones, the nerve cells that supply all voluntary muscle activity.
Lead researcher, Dr Stan Burgess from the University of Leeds' Faculty of Biological Sciences, says: "Motor neurones have a very complex transportation system. While the nuclei of motor neurones lie within the spinal cord, they have branches that can run the entire length of a limb, say from the spine to the big toe. This branch is like a highway for molecular motors such as dynein. If there's a disruption to the traffic, it can lead to cell death and eventually to muscular weakness, characterised in diseases such as motor neurone disease."
Measuring only 50 nanometers, dynein can carry its cargo up to a metre in humans - the equivalent of humans walking about forty thousand kilometres. Dynein is poorly understood, partly because it is difficult to engineer for experimental studies and because the usual techniques for determining the structure of a molecule – X-ray crystallography and nuclear magnetic resonance spectroscopy (NMR) - have been unsuccessful.
The Leeds team worked with synthetic dynein engineered by their Japanese colleagues which contained fluorescent marker proteins at key points within the motor. Using an electron microscope, they were able to plot the positions of the marker proteins both with and without ATP, the 'fuel' that drives the motor.
Dr Burgess says: "Dynein, like all proteins, is a long linear molecule folded up into a complicated three-dimensional structure. While we can't solve the atomic structure using electron-microscopy, our research has enabled us to map key points in the chain and see which parts of it move."
Co-researcher Anthony Roberts, says: "Seeing the molecule change shape with ATP gives us clues to its motor mechanism that we will follow up in future work."
The Japanese scientists also removed the ends of the dynein molecule to expose the core, and imaging at Leeds showed that – contrary to the accepted model – the core of dynein is similar to other ring-shaped molecular machines in the cell, with which dynein shares distant evolutionary links.
"There has been disagreement over the structure of dynein within the scientific community, and both elements of our research – identifying the moving parts and revealing the structure of the core – has meant we can correct some of the mistaken ideas," says Dr Burgess. "Hopefully this will enable future research on this very important protein to move forward much faster."
The researchers from Leeds and Tokyo have already joined forces with colleagues in Ljubljana, Slovenia, to secure a grant of US$1.2 million from the prestigious Human Frontier Science Program (HFSP) to continue their research on dynein. Their bid was ranked first among 18 awards made from 600 original applications from around the world.
Headed by Dr Burgess, the international team will build on their latest findings and their expertise in engineering and imaging dynein. They aim to study the structure of two-headed dynein walking along its microtubule track using electron microscopy. Colleagues in Tokyo will measure the force it exerts as it walks as well as its step size and speed. The team in Slovenia will then combine all the new data into a computer model to simulate the movement of the protein.
"By examining the structure and mechanism of dynein while it's moving, we hope to learn more about how the protein works in the cell, so we can better understand what happens when it goes wrong," says Dr Burgess.
Jo Kelly | EurekAlert!
Further reports about: > Biological Sciences Research > Cells > Molecule > Neurone > X-ray crystallography > cell death > dynein > dynein's structure > motor neurone disease > motor neurones > motor protein > nerve cells > nuclear magnetic resonance spectroscopy > progressive neurological disorders > transporting molecular cargo
Modern genetic sequencing tools give clearer picture of how corals are related
17.08.2017 | University of Washington
The irresistible fragrance of dying vinegar flies
16.08.2017 | Max-Planck-Institut für chemische Ökologie
Whether you call it effervescent, fizzy, or sparkling, carbonated water is making a comeback as a beverage. Aside from quenching thirst, researchers at the University of Illinois at Urbana-Champaign have discovered a new use for these "bubbly" concoctions that will have major impact on the manufacturer of the world's thinnest, flattest, and one most useful materials -- graphene.
As graphene's popularity grows as an advanced "wonder" material, the speed and quality at which it can be manufactured will be paramount. With that in mind,...
Physicists at the University of Bonn have managed to create optical hollows and more complex patterns into which the light of a Bose-Einstein condensate flows. The creation of such highly low-loss structures for light is a prerequisite for complex light circuits, such as for quantum information processing for a new generation of computers. The researchers are now presenting their results in the journal Nature Photonics.
Light particles (photons) occur as tiny, indivisible portions. Many thousands of these light portions can be merged to form a single super-photon if they are...
For the first time, scientists have shown that circular RNA is linked to brain function. When a RNA molecule called Cdr1as was deleted from the genome of mice, the animals had problems filtering out unnecessary information – like patients suffering from neuropsychiatric disorders.
While hundreds of circular RNAs (circRNAs) are abundant in mammalian brains, one big question has remained unanswered: What are they actually good for? In the...
An experimental small satellite has successfully collected and delivered data on a key measurement for predicting changes in Earth's climate.
The Radiometer Assessment using Vertically Aligned Nanotubes (RAVAN) CubeSat was launched into low-Earth orbit on Nov. 11, 2016, in order to test new...
A study led by scientists of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg presents evidence of the coexistence of superconductivity and “charge-density-waves” in compounds of the poorly-studied family of bismuthates. This observation opens up new perspectives for a deeper understanding of the phenomenon of high-temperature superconductivity, a topic which is at the core of condensed matter research since more than 30 years. The paper by Nicoletti et al has been published in the PNAS.
Since the beginning of the 20th century, superconductivity had been observed in some metals at temperatures only a few degrees above the absolute zero (minus...
16.08.2017 | Event News
04.08.2017 | Event News
26.07.2017 | Event News
17.08.2017 | Physics and Astronomy
17.08.2017 | Earth Sciences
17.08.2017 | Physics and Astronomy