Nav: Home

Unique protein partly to blame for worm's digestive distress

March 06, 2017

A protein unlike any other appears to be partially responsible for upsetting the stomachs of the most common animal on the planet.

Results of a Rice University study of the Orsay virus unique to nematodes, the worms that make up 80 percent of living creatures on Earth, have revealed the molecular structure of a fusion protein that forms unusual fibers and attaches the virus to cells and infects them.

The researchers led by structural biologist Yizhi Jane Tao and geneticist Weiwei Zhong said the protein is the first pentameric fiber with potential antiviral applications. They hope it will guide bioengineers as they develop synthetic variations of the virus that can infect new worm hosts, including the parasitic ones that infect humans and animals.

Their research is detailed in the open-access journal PLOS Pathogens.

The Orsay virus, the first known to infect Caenorhabditis elegans, was discovered in France in 2011. It doesn't kill the worm, but infects its digestive tract. Three years ago, the Rice researchers won a race to detail the complete crystal structure of the virus -- a key step in figuring out its mechanism -- and then won a major National Institutes of Health grant to study it.

What they call the delta protein is one of three proteins that make up the Orsay virus. The others are the viral capsid shell and the RNA-dependent RNA polymerase (RdRP) that are responsible for protecting and replicating the viral genome, respectively. The protruding delta protein appears to be responsible for binding the virus to the surface of cells, which enables infection.

That function isn't unique, but the protein's form is out of the ordinary, Tao said. Immediately upon expression, individual delta units gather into five-unit fibers known as pentameric proteins that extend the reach of the virus well beyond the capsid and allows them to probe for receptor targets on cells.

The fibers can also exist as stand-alone units that show promise for disrupting infectious disease. The researchers synthesized free-floating pentameric delta fibers and fed them to C. elegans, where they quickly filled cell-receptor sites. When the researchers exposed these worms to Orsay, the virus was unable to deliver its infectious load.

The researchers did not find single delta subunits in cells, which suggested the proteins are programmed to assemble into only five-unit fibers. While protein fibers are not uncommon for viruses, Tao said this is the first molecule that was found to form pentameric fibers.

Lead authors and Rice graduate students Yanlin Fan and Yusong Guo not only detailed the protein's homogenous structure but also captured electron microscope images of the ultrafine spikes they produce.

"The virus only encodes three proteins, so we knew this one must be important," said Tao, whose lab analyzes the structure and function of molecules through X-ray crystallography and electron microscopy. "By studying Orsay's replication cycle, we learned that it's a receptor binding protein. The virus first has to recognize a permissive host and get into the cell, and this protein carries out that function."

Zhong said lab-created mutants of the virus that lacked the fiber could not infect worms. In another experiment, the researchers found that free-floating delta protein fibers would bind to receptors on the worms' cells, also protecting them. "Ying just doped the worms with delta proteins, which saturated and locked the receptors," she said. "Then she added the virus, which was unable to infect them."

Zhong noted that since the discovery of Orsay's ability to infect C. elegans, two related viruses called Santeul and LeBlanc have been found to infect a similar nematode, C. briggsae. All cause intestinal symptoms without killing the worm, she said, but tests showed Orsay does not infect C. briggsae, nor do Santeul and LeBlanc infect C. elegans.

Structural details of the unusual protein could help bioengineers synthesize custom versions to generate new viruses to target parasitic worms, Zhong said. "By studying the binding tip of the fiber, maybe we can figure out why the delta recognizes specific species of worms," she said.

The next step will be to figure out how the viral payload gets into cells, where Orsay is replicated - and then how it gets out to infect others. "But finding this binding protein is a good start," Tao said. "It's novel and it's eye-opening."
-end-
Co-authors of the paper are former Rice graduate student Yusong Guo, postdoctoral researcher Wang Yuan and current postdoctoral researcher Ying Zhou; graduate student Matthew Holt, postdoctoral associate Tao Wang and Nicolas Young, an assistant professor of biochemistry and molecular biology, all at Baylor College of Medicine; and Borries Demeler, an assistant professor of biochemistry at the University of Texas Health Science Center at San Antonio.

The Robert A. Welch Foundation, the Hamill Foundation, the Kresge Science Initiative Endowment Fund at Rice, the National Institutes of Health and the National Science Foundation supported the research.

Read the abstract at http://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1006231

This news release can be found online at http://news.rice.edu/2017/03/06/orm-ways-orsay-ummy-tay-unique-protein-partly-to-blame/

Follow Rice News and Media Relations via Twitter @RiceUNews

Related materials:

The Tao Laboratory: http://www.bioc.rice.edu/~ytao/

Zhong Lab: http://wormlab.rice.edu

Nicolas Young Lab: http://www.bcm.edu/research/labs/nicolas-young

Wiess School of Natural Sciences: http://natsci.rice.edu

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 3,879 undergraduates and 2,861 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 is ranked No. 1 for happiest students and for lots of race/class interaction by the Princeton Review. Rice is also rated as a best value among private universities by Kiplinger's Personal Finance. To read "What they're saying about Rice," go to http://tinyurl.com/RiceUniversityoverview.

Rice University

Related Proteins Articles:

Discovering, counting, cataloguing proteins
Scientists describe a well-defined mitochondrial proteome in baker's yeast.
Interrogating proteins
Scientists from the University of Bristol have designed a new protein structure, and are using it to understand how protein structures are stabilized.
Ancient proteins studied in detail
How did protein interactions arise and how have they developed?
What can we learn from dinosaur proteins?
Researchers recently confirmed it is possible to extract proteins from 80-million-year-old dinosaur bones.
Relocation of proteins with a new nanobody tool
Researchers at the Biozentrum of the University of Basel have developed a new method by which proteins can be transported to a new location in a cell.
Proteins that can take the heat
Ancient proteins may offer clues on how to engineer proteins that can withstand the high temperatures required in industrial applications, according to new research published in the Proceedings of the National Academy of Sciences.
Designer proteins fold DNA
Florian Praetorius and Professor Hendrik Dietz of the Technical University of Munich have developed a new method that can be used to construct custom hybrid structures using DNA and proteins.
The proteins that domesticated our genomes
EPFL scientists have carried out a genomic and evolutionary study of a large and enigmatic family of human proteins, to demonstrate that it is responsible for harnessing the millions of transposable elements in the human genome.
Rare proteins collapse earlier
Some organisms are able to survive in hot springs, while others can only live at mild temperatures because their proteins aren't able to withstand such extreme heat.
How proteins reshape cell membranes
Small 'bubbles' frequently form on membranes of cells and are taken up into their interior.

Related Proteins Reading:

Best Science Podcasts 2019

We have hand picked the best science podcasts for 2019. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Anthropomorphic
Do animals grieve? Do they have language or consciousness? For a long time, scientists resisted the urge to look for human qualities in animals. This hour, TED speakers explore how that is changing. Guests include biological anthropologist Barbara King, dolphin researcher Denise Herzing, primatologist Frans de Waal, and ecologist Carl Safina.
Now Playing: Science for the People

#SB2 2019 Science Birthday Minisode: Mary Golda Ross
Our second annual Science Birthday is here, and this year we celebrate the wonderful Mary Golda Ross, born 9 August 1908. She died in 2008 at age 99, but left a lasting mark on the science of rocketry and space exploration as an early woman in engineering, and one of the first Native Americans in engineering. Join Rachelle and Bethany for this very special birthday minisode celebrating Mary and her achievements. Thanks to our Patreons who make this show possible! Read more about Mary G. Ross: Interview with Mary Ross on Lash Publications International, by Laurel Sheppard Meet Mary Golda...