Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

New malaria protein structure upends theory of how cells grow and move

31.05.2011
Researchers from the Walter and Eliza Hall Institute have overturned conventional wisdom on how cell movement across all species is controlled, solving the structure of a protein that cuts power to the cell 'motor'. The protein could be a potential drug target for future malaria and anti-cancer treatments.

By studying the structure of actin-depolymerising factor 1 (ADF1), a key protein involved in controlling the movement of malaria parasites, the researchers have demonstrated that scientists' decades-long understanding of the relationship between protein structure and cell movement is flawed.

Dr Jake Baum and Mr Wilson Wong from the institute's Infection and Immunity division and Dr Jacqui Gulbis from the Structural Biology division, in collaboration with Dr Dave Kovar from the University of Chicago, US, led the research, which appears in today's edition of the Proceedings of the National Academy of Sciences USA.

Dr Baum said actin-depolymerising factors (ADFs) and their genetic regulators have long been known to be involved in controlling cell movement, including the movement of malaria parasites and movement of cancer cells through the body. Anti-cancer treatments that exploit this knowledge are under development.

"ADFs help the cell to recycle actin, a protein which controls critical functions such as cell motility, muscle contraction, and cell division and signaling," Dr Baum said. "Actin has unusual properties, being able to spontaneously form polymers which are used by cells to engage internal molecular motors – much like a clutch does in the engine of your car. A suite of accessory proteins control how the clutch is engaged, including those that dismantle or 'cut' these polymers, such as ADF1.

"For many years research in yeast, plants and humans has suggested that the ability of ADFs to dismantle actin polymers – effectively disengaging the clutch – required a small molecular 'finger' to break the actin in two," Dr Baum said. "However, when we looked at the malaria ADF1 protein, we were surprised to discover that it lacked this molecular 'finger', yet remarkably was still able to cut the polymers. We discovered that a previously overlooked part of the protein, effectively the 'knuckle' of the finger-like protrusion, was responsible for dismantling the actin; we then discovered this 'hidden' domain was present across all ADFs."

Mr Wong said that the Australian Synchrotron was critical in providing the extraordinary detail that helped the team pinpoint the protein 'knuckle'. "This is the first time a 3D image of the ADF protein has been captured in such detail from any cell type," Mr Wong said. "Imaging the protein structure at such high resolution was critical in proving beyond question the segment of the protein responsible for cutting actin polymers. Obtaining that image would have been impossible without the synchrotron facilities."

Dr Baum said the new knowledge will give researchers a much clearer understanding of one of the fundamental steps governing how cells across all species grow, divide and, importantly, move. "Knowing that this one small segment of the protein is singularly responsible for ADF1 function means that we need to focus on an entirely new target not only for developing anti-malarial treatments, but also other diseases where potential treatments target actin, such as anti-cancer therapeutics," Dr Baum said. "Malaria researchers are normally used to following insights from other biological systems; this is a case of the exception proving the rule: where the malaria parasite, being so unusual, reveals how all other ADFs across nature work."

More than 250 million people contract malaria each year, and almost one million people, mostly children, die from the disease. The malaria parasite has developed resistance to most of the therapeutic agents available for treating the disease, so identifying novel ways of targeting the parasite is crucial.

Dr Baum said that the discovery could lead to development of drugs entirely geared toward preventing malaria infection, without adverse effects on human cells. "One of the primary goals of the global fight against malaria is to develop novel drugs that prevent infection and transmission in all hosts, to break the malaria cycle," Dr Baum said. "There is a very real possibility that, in the future, drugs could be developed that 'jam' this molecular 'clutch', meaning the malaria parasite cannot move and continue to infect cells in any of its conventional hosts, which would be a huge breakthrough for the field."

This project was funded by the National Health and Medical Research Council (NHMRC).

Liz Williams | EurekAlert!
Further information:
http://www.wehi.edu.au

More articles from Life Sciences:

nachricht Immune Defense Without Collateral Damage
23.01.2017 | Universität Basel

nachricht The interactome of infected neural cells reveals new therapeutic targets for Zika
23.01.2017 | D'Or Institute for Research and Education

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Quantum optical sensor for the first time tested in space – with a laser system from Berlin

For the first time ever, a cloud of ultra-cold atoms has been successfully created in space on board of a sounding rocket. The MAIUS mission demonstrates that quantum optical sensors can be operated even in harsh environments like space – a prerequi-site for finding answers to the most challenging questions of fundamental physics and an important innovation driver for everyday applications.

According to Albert Einstein's Equivalence Principle, all bodies are accelerated at the same rate by the Earth's gravity, regardless of their properties. This...

Im Focus: Traffic jam in empty space

New success for Konstanz physicists in studying the quantum vacuum

An important step towards a completely new experimental access to quantum physics has been made at University of Konstanz. The team of scientists headed by...

Im Focus: How gut bacteria can make us ill

HZI researchers decipher infection mechanisms of Yersinia and immune responses of the host

Yersiniae cause severe intestinal infections. Studies using Yersinia pseudotuberculosis as a model organism aim to elucidate the infection mechanisms of these...

Im Focus: Interfacial Superconductivity: Magnetic and superconducting order revealed simultaneously

Researchers from the University of Hamburg in Germany, in collaboration with colleagues from the University of Aarhus in Denmark, have synthesized a new superconducting material by growing a few layers of an antiferromagnetic transition-metal chalcogenide on a bismuth-based topological insulator, both being non-superconducting materials.

While superconductivity and magnetism are generally believed to be mutually exclusive, surprisingly, in this new material, superconducting correlations...

Im Focus: Studying fundamental particles in materials

Laser-driving of semimetals allows creating novel quasiparticle states within condensed matter systems and switching between different states on ultrafast time scales

Studying properties of fundamental particles in condensed matter systems is a promising approach to quantum field theory. Quasiparticles offer the opportunity...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Sustainable Water use in Agriculture in Eastern Europe and Central Asia

19.01.2017 | Event News

12V, 48V, high-voltage – trends in E/E automotive architecture

10.01.2017 | Event News

2nd Conference on Non-Textual Information on 10 and 11 May 2017 in Hannover

09.01.2017 | Event News

 
Latest News

Tracking movement of immune cells identifies key first steps in inflammatory arthritis

23.01.2017 | Health and Medicine

Electrocatalysis can advance green transition

23.01.2017 | Physics and Astronomy

New technology for mass-production of complex molded composite components

23.01.2017 | Process Engineering

VideoLinks
B2B-VideoLinks
More VideoLinks >>>