Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Biologists take snapshot of fleeting protein process

31.05.2013
Rice, BCM crystallographers capture elusive actin nucleation process

Structural biologists from Rice University and Baylor College of Medicine (BCM) have captured the first three-dimensional crystalline snapshot of a critical but fleeting process that takes place thousands of times per second in each human cell. The research appears online today in the journal Cell Reports and could prove useful in the study of cancer and other diseases.


To decipher the structure of the F-actin nucleus, researchers used a dual-mutant strategy. They created two mutant versions of actin monomers that could bind together to form a nucleus but could not bind with additional monomers to form the F-actin polymer chain.

Credit: J. Ma/Rice University

The biological "freeze-frame" shows the initial step in the formation of actin, a sturdy strand-like filament that is vital for humans. Actin filaments help cells maintain their shape. The filaments, which are called F-actin, also play key roles in muscle contraction, cell division and other critical processes.

"One of the major distinctions between cancerous cells and healthy cells is their shape," said study co-author Jianpeng Ma, professor of bioengineering at Rice and the Lodwick T. Bolin Professor of Biochemistry at BCM. "There is a correlation between healthy shape and well-regulated cell growth, and cancer cells are often ugly and ill-shaped compared to healthy cells."

F-actin was discovered in 1887, but despite the more than 18,000 actin-related studies in scientific literature, biologists have struggled to unlock some of its secrets. For example, F-actin is a polymer made of many smaller proteins called monomers. These building blocks, which are called G-actin, self-assemble end to end to form F-actin. But the self-assembly process is so efficient that scientists have been unable to see what happens when the first two or three monomers come together to form the nucleus of a filament. The F-actin filaments inside cells are constantly being built, torn apart and rebuilt.

"Nucleation is critical for this continual building and rebuilding," said BCM biochemist and study co-author Qinghua Wang. "For healthy cells, nucleation is the starting place for robust shape. For unhealthy cells, like cancer, nucleation processes may play a crucial role in unregulated growth. That's one reason we want to better understand nucleation."

In 2008, Ma and Wang asked Xiaorui Chen, a graduate student in BCM's Structural and Computational Biology and Molecular Biophysics program, to undertake the task of using x-ray crystallography to determine the structure of the actin nucleus. Her initial attempts failed, but the team finally hit upon the winning idea of creating two mutant versions of G-actin that could nucleate but not polymerize.

Native G-actin binds with one neighbor on top and one on bottom, and this top-bottom, end-to-end binding pattern is the key to forming long F-actin polymers. To foster nucleation without polymerization, Chen created two mutant versions of G-actin. One mutant could bind normally on top but not on bottom, and the other could bind normally on bottom but not on top.

"This dual-mutant strategy was the key," said Chen, who is now a postdoctoral researcher at BCM. "After that, we had to overcome problems related to forming and growing the crystal samples needed for crystallography."

Chen used a two-stage process to prepare the crystals. She first used high levels of super-saturation to spur initial crystal formation and then used a process called seeding to transfer the newly formed crystals to another medium where they could grow large enough for examination.

Once the crystals were prepared, they were analyzed with x-ray diffraction, which revealed the atomic arrangement of each atom in the nucleated, dual-mutant pair. "We believe this dual-mutant arrangement reveals the most critical contacts involved in nucleation," Ma said. "For the first time, we are able to see how actin nucleation begins."

Additional co-authors include Fengyun Ni of both Rice and BCM, Xia Tian of BCM and Elena Kondrashkina of Northwestern University. The research was supported by the National Institutes of Health, the Gillson-Longenbaugh Foundation, the National Science Foundation, the Welch Foundation, the Department of Energy and the Michigan Economic Development Corp.

A copy of the Cell Reports article is available at: http://www.cell.com/cell-reports/fulltext/S2211-1247(13)00210-6

Follow Rice News and Media Relations via Twitter @RiceUNews

Located on a 300-acre forested campus in Houston, Rice University is consistently ranked among the nation's top 20 universities by U.S. News & World Report. Rice has highly respected schools of Architecture, Business, Continuing Studies, Engineering, Humanities, Music, Natural Sciences and Social Sciences and is home to the Baker Institute for Public Policy. With 3,708 undergraduates and 2,374 graduate students, Rice's undergraduate student-to-faculty ratio is 6-to-1. Its residential college system builds close-knit communities and lifelong friendships, just one reason why Rice has been ranked No. 1 for best quality of life multiple times by the Princeton Review and No. 2 for "best value" among private universities by Kiplinger's Personal Finance. To read "What they're saying about Rice," go to http://tinyurl.com/AboutRiceU.

David Ruth | EurekAlert!
Further information:
http://www.rice.edu

More articles from Life Sciences:

nachricht Warming ponds could accelerate climate change
21.02.2017 | University of Exeter

nachricht An alternative to opioids? Compound from marine snail is potent pain reliever
21.02.2017 | University of Utah

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Breakthrough with a chain of gold atoms

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

Im Focus: DNA repair: a new letter in the cell alphabet

Results reveal how discoveries may be hidden in scientific “blind spots”

Cells need to repair damaged DNA in our genes to prevent the development of cancer and other diseases. Our cells therefore activate and send “repair-proteins”...

Im Focus: Dresdner scientists print tomorrow’s world

The Fraunhofer IWS Dresden and Technische Universität Dresden inaugurated their jointly operated Center for Additive Manufacturing Dresden (AMCD) with a festive ceremony on February 7, 2017. Scientists from various disciplines perform research on materials, additive manufacturing processes and innovative technologies, which build up components in a layer by layer process. This technology opens up new horizons for component design and combinations of functions. For example during fabrication, electrical conductors and sensors are already able to be additively manufactured into components. They provide information about stress conditions of a product during operation.

The 3D-printing technology, or additive manufacturing as it is often called, has long made the step out of scientific research laboratories into industrial...

Im Focus: Mimicking nature's cellular architectures via 3-D printing

Research offers new level of control over the structure of 3-D printed materials

Nature does amazing things with limited design materials. Grass, for example, can support its own weight, resist strong wind loads, and recover after being...

Im Focus: Three Magnetic States for Each Hole

Nanometer-scale magnetic perforated grids could create new possibilities for computing. Together with international colleagues, scientists from the Helmholtz Zentrum Dresden-Rossendorf (HZDR) have shown how a cobalt grid can be reliably programmed at room temperature. In addition they discovered that for every hole ("antidot") three magnetic states can be configured. The results have been published in the journal "Scientific Reports".

Physicist Dr. Rantej Bali from the HZDR, together with scientists from Singapore and Australia, designed a special grid structure in a thin layer of cobalt in...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Booth and panel discussion – The Lindau Nobel Laureate Meetings at the AAAS 2017 Annual Meeting

13.02.2017 | Event News

Complex Loading versus Hidden Reserves

10.02.2017 | Event News

International Conference on Crystal Growth in Freiburg

09.02.2017 | Event News

 
Latest News

Impacts of mass coral die-off on Indian Ocean reefs revealed

21.02.2017 | Earth Sciences

Novel breast tomosynthesis technique reduces screening recall rate

21.02.2017 | Medical Engineering

Use your Voice – and Smart Homes will “LISTEN”

21.02.2017 | Trade Fair News

VideoLinks
B2B-VideoLinks
More VideoLinks >>>