Navigation Links
New malaria protein structure upends theory of how cells grow and move
Date:5/30/2011

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."


'/>"/>

Contact: Liz Williams
williams@wehi.edu.au
61-405-279-095
Walter and Eliza Hall Institute
Source:Eurekalert  

Related biology news :

1. 2020 vision of vaccines for malaria, TB and HIV/AIDS
2. Top Australian malaria researcher elected Fellow of the Royal Society
3. Malaria against malaria: A pre-existing malaria infection can prevent a second infection
4. €12 million ($16.9 million) project to develop new tools for malaria control
5. Insight into parasite family planning could help target malaria
6. Antifungal compound found on tropical seaweed has promising antimalarial properties
7. Floating spores kill malaria mosquito larvae
8. University of South Florida and Draper team to create advanced devices for testing malaria drugs
9. Malaria medication may help against 1 type of frontotemporal dementia
10. Malaria modeling and control focus of workshop
11. Malaria-infected cells stiffen, block blood flow
Post Your Comments:
*Name:
*Comment:
*Email:
Related Image:
New malaria protein structure upends theory of how cells grow and move
(Date:3/18/2016)... , March 18, 2016 ... Suppliers of Biometrics, ICT, Manned & Unmanned Vehicles, Physical infrastructure ... & security companies in the border security market and the ... and Europe has led visiongain ... companies improved success. --> defence & security ...
(Date:3/15/2016)... -- --> --> According ... "Digital Door Lock Systems Market - Global Industry Analysis, Size, ... digital door lock systems market in terms of revenue was ... to grow at a CAGR of 31.8% during the period ... (MSMEs) across the world and high industrial activity driving inclusive ...
(Date:3/14/2016)... Florida , March 14, 2016 ... the growing mobile commerce market, announces the airing of a ... channels starting the week of March 21 st .  The ... CNBC, including its popular Squawk on the Street show. ... focused on the growing mobile commerce market, announces the airing ...
Breaking Biology News(10 mins):
(Date:4/28/2016)... York, NY (PRWEB) , ... April 28, 2016 ... ... QuickSTAT has made significant investments in recruiting top industry experts, and expanding its ... Platform, which provides industry-leading tools for clients to manage their clinical trial projects. ...
(Date:4/27/2016)... York, NY (PRWEB) , ... April 27, 2016 ... ... realizing it. Touch screen mobile devices with fingerprint recognition for secure access, ... libraries are only a few ways consumers are interacting with biometrics technology today. ...
(Date:4/27/2016)... Baltimore, MD (PRWEB) , ... April 27, 2016 ... ... appointed Greg Lamka, PhD to its Scientific Advisory Board. Dr. Lamka will assist ... of plant pathogen detection. , PathSensors deploys the CANARY® test platform for ...
(Date:4/27/2016)... , April 27, 2016 ... report with specific focus on US, EU, ... , to the healthcare business intelligence collection ... Complete report on the Flow Cytometry ... and supported with 282 tables and figures is ...
Breaking Biology Technology: