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."
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.
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."
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!
From a plant sugar to toxic hydrogen sulfide
19.12.2018 | Universität Konstanz
Gut microbiome regulates the intestinal immune system, researchers find
19.12.2018 | Brown University
Different eras of civilization are defined by the discovery of new materials, as new materials drive new capabilities. And yet, identifying the best material...
Researchers from the University of Basel have reported a new method that allows the physical state of just a few atoms or molecules within a network to be controlled. It is based on the spontaneous self-organization of molecules into extensive networks with pores about one nanometer in size. In the journal ‘small’, the physicists reported on their investigations, which could be of particular importance for the development of new storage devices.
Around the world, researchers are attempting to shrink data storage devices to achieve as large a storage capacity in as small a space as possible. In almost...
The more objects we make "smart," from watches to entire buildings, the greater the need for these devices to store and retrieve massive amounts of data quickly without consuming too much power.
Millions of new memory cells could be part of a computer chip and provide that speed and energy savings, thanks to the discovery of a previously unobserved...
What if, instead of turning up the thermostat, you could warm up with high-tech, flexible patches sewn into your clothes - while significantly reducing your...
A widely used diabetes medication combined with an antihypertensive drug specifically inhibits tumor growth – this was discovered by researchers from the University of Basel’s Biozentrum two years ago. In a follow-up study, recently published in “Cell Reports”, the scientists report that this drug cocktail induces cancer cell death by switching off their energy supply.
The widely used anti-diabetes drug metformin not only reduces blood sugar but also has an anti-cancer effect. However, the metformin dose commonly used in the...
12.12.2018 | Event News
10.12.2018 | Event News
06.12.2018 | Event News
19.12.2018 | Information Technology
19.12.2018 | Physics and Astronomy
19.12.2018 | Life Sciences