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 Two Group A Streptococcus genes linked to 'flesh-eating' bacterial infections
25.09.2017 | University of Maryland

nachricht Rainbow colors reveal cell history: Uncovering β-cell heterogeneity
22.09.2017 | DFG-Forschungszentrum für Regenerative Therapien TU Dresden

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: LaserTAB: More efficient and precise contacts thanks to human-robot collaboration

At the productronica trade fair in Munich this November, the Fraunhofer Institute for Laser Technology ILT will be presenting Laser-Based Tape-Automated Bonding, LaserTAB for short. The experts from Aachen will be demonstrating how new battery cells and power electronics can be micro-welded more efficiently and precisely than ever before thanks to new optics and robot support.

Fraunhofer ILT from Aachen relies on a clever combination of robotics and a laser scanner with new optics as well as process monitoring, which it has developed...

Im Focus: The pyrenoid is a carbon-fixing liquid droplet

Plants and algae use the enzyme Rubisco to fix carbon dioxide, removing it from the atmosphere and converting it into biomass. Algae have figured out a way to increase the efficiency of carbon fixation. They gather most of their Rubisco into a ball-shaped microcompartment called the pyrenoid, which they flood with a high local concentration of carbon dioxide. A team of scientists at Princeton University, the Carnegie Institution for Science, Stanford University and the Max Plank Institute of Biochemistry have unravelled the mysteries of how the pyrenoid is assembled. These insights can help to engineer crops that remove more carbon dioxide from the atmosphere while producing more food.

A warming planet

Im Focus: Highly precise wiring in the Cerebral Cortex

Our brains house extremely complex neuronal circuits, whose detailed structures are still largely unknown. This is especially true for the so-called cerebral cortex of mammals, where among other things vision, thoughts or spatial orientation are being computed. Here the rules by which nerve cells are connected to each other are only partly understood. A team of scientists around Moritz Helmstaedter at the Frankfiurt Max Planck Institute for Brain Research and Helene Schmidt (Humboldt University in Berlin) have now discovered a surprisingly precise nerve cell connectivity pattern in the part of the cerebral cortex that is responsible for orienting the individual animal or human in space.

The researchers report online in Nature (Schmidt et al., 2017. Axonal synapse sorting in medial entorhinal cortex, DOI: 10.1038/nature24005) that synapses in...

Im Focus: Tiny lasers from a gallery of whispers

New technique promises tunable laser devices

Whispering gallery mode (WGM) resonators are used to make tiny micro-lasers, sensors, switches, routers and other devices. These tiny structures rely on a...

Im Focus: Ultrafast snapshots of relaxing electrons in solids

Using ultrafast flashes of laser and x-ray radiation, scientists at the Max Planck Institute of Quantum Optics (Garching, Germany) took snapshots of the briefest electron motion inside a solid material to date. The electron motion lasted only 750 billionths of the billionth of a second before it fainted, setting a new record of human capability to capture ultrafast processes inside solids!

When x-rays shine onto solid materials or large molecules, an electron is pushed away from its original place near the nucleus of the atom, leaving a hole...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

“Lasers in Composites Symposium” in Aachen – from Science to Application

19.09.2017 | Event News

I-ESA 2018 – Call for Papers

12.09.2017 | Event News

EMBO at Basel Life, a new conference on current and emerging life science research

06.09.2017 | Event News

 
Latest News

An international team of physicists a coherent amplification effect in laser excited dielectrics

25.09.2017 | Physics and Astronomy

LaserTAB: More efficient and precise contacts thanks to human-robot collaboration

25.09.2017 | Trade Fair News

Highest-energy cosmic rays have extragalactic origin

25.09.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>