Featured Research

from universities, journals, and other organizations

Researchers Determine 3D Structure Of Key Bacterial Protein

Date:
October 12, 1999
Source:
Howard Hughes Medical Institute
Summary:
Researchers from the Howard Hughes Medical Institute (HHMI) have determined the three-dimensional structure of invasin, a protein that allows a close relative of the bubonic plague bacterium to infect intestinal cells and cause food poisoning.

October 7, 1999 – Researchers from the Howard Hughes Medical Institute (HHMI) have determined the three-dimensional structure of invasin, a protein that allows a close relative of the bubonic plague bacterium to infect intestinal cells and cause food poisoning.

When the bacterium Yersinia pseudotuberculosis is consumed in contaminated food, it gains access to certain cells in the intestinal epithelium called M cells. Once inside the intestines, Y. pseudotuberculosis, which is related to the organism that causes bubonic plague, binds to receptors on M cells. This leads to the entry of the bacteria into regional lymph nodes in the intestine. The growth of bacterial colonies in the lymph nodes triggers intense nausea, vomiting and diarrhea. It turns out that invasin is crucial to the bacterium's ability to establish a foothold in the lymph nodes, says Ralph Isberg, an HHMI investigator at Tufts University School of Medicine.

When Isberg first began studying Y. pseudotuberculosis in the 1980s, "there was very little known about how any bacterium was able to enter into an animal cell and trigger infection," he said.

To better understand how Y. pseudotuberculosis causes illness, Isberg set about cloning genes from Y. pseudotuberculosis and inserting them one by one into a second bacterium used frequently in laboratory research. He realized he had made an important discovery when a strain of the laboratory bacterium harboring a single Y. pseudotuberculosis gene had acquired the ability to enter animal cells. "This single gene (inv), and the invasin protein it coded for, was sufficient for infection of cells in culture," Isberg said.

Researchers now know that the aptly named bacterial protein binds more tightly to integrins — the receptors for invasin — than do other proteins, or ligands. To learn how invasin out-competes the natural ligands for their place on the receptors, Isberg and HHMI research assistant Michele Brown collaborated with HHMI structural biologist Pamela Bjorkman and graduate student Zsuzsa Hamburger, both of whom are at the California Institute of Technology. Bjorkman and Hamburger crystallized the invasin protein and used x-ray diffraction techniques to determine its three-dimensional structure. The researchers published their work in the October 8, 1999, issue of the journal Science.

The three-dimensional structure reveals that invasin is a rod-like protein resembling five tandemly arranged beads. In comparing invasin to one of the integrins' natural ligands, called fibronectins, Bjorkman and her colleagues found that the two types of proteins share some structural features, such as an extended structure and a similar distribution of key binding residues, but are otherwise quite different in their folding topologies.

"It seems that the bacteria got the essence of what's needed to bind to an integrin, but they did it in their own way," Bjorkman said. "Invasin basically distilled out the important features for integrin binding, then put them into a different folding context."

There are antibiotics available that can kill Y. pseudotuberculosis, but Bjorkman and Isberg say that structural information about invasin, and proteins from other types of bacteria that are "modeled on" invasin, may lead to better antibacterial agents. "We now have a more specific target," said Isberg.

A drug that blocks binding to crucial regions of the invasin receptors should be able to prevent the bacterium from entering a cell, Isberg said. Also, knowing where both invasin and fibronectin bind to integrins gives scientists a new tool to explore ways of altering integrin function.

With the structure of invasin solved, Isberg and his colleagues plan to look more closely at the messages the cell receives when invasin binds to its integrin receptors. They are also interested in the process by which this binding triggers uptake of the bacteria by epithelial cells in the intestine.

Meanwhile, the next step for Bjorkman and her colleagues is to determine the structure of invasin and an integrin bound together. Both efforts should offer additional insight into the way cells talk to each other and the way bacteria cause disease.

Bjorkman believes that similarities in the structures of invasin and fibronectin suggest the bacterial and host proteins bind to integrins in a similar way. "Choosing an integrin as a receptor and copying the way a host protein binds to it ensures that the bacteria can infect its host," Bjorkman said. "Host cells need integrins, so they cannot be changed to avoid binding invasin since that would disrupt important host functions."


Story Source:

The above story is based on materials provided by Howard Hughes Medical Institute. Note: Materials may be edited for content and length.


Cite This Page:

Howard Hughes Medical Institute. "Researchers Determine 3D Structure Of Key Bacterial Protein." ScienceDaily. ScienceDaily, 12 October 1999. <www.sciencedaily.com/releases/1999/10/991012075346.htm>.
Howard Hughes Medical Institute. (1999, October 12). Researchers Determine 3D Structure Of Key Bacterial Protein. ScienceDaily. Retrieved July 23, 2014 from www.sciencedaily.com/releases/1999/10/991012075346.htm
Howard Hughes Medical Institute. "Researchers Determine 3D Structure Of Key Bacterial Protein." ScienceDaily. www.sciencedaily.com/releases/1999/10/991012075346.htm (accessed July 23, 2014).

Share This




More Health & Medicine News

Wednesday, July 23, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Idaho Boy Helps Brother With Disabilities Complete Triathlon

Idaho Boy Helps Brother With Disabilities Complete Triathlon

Newsy (July 23, 2014) An 8-year-old boy helped his younger brother, who has a rare genetic condition that's confined him to a wheelchair, finish a triathlon. Video provided by Newsy
Powered by NewsLook.com
Stone Fruit Listeria Scare Causes Sweeping Recall

Stone Fruit Listeria Scare Causes Sweeping Recall

Newsy (July 22, 2014) The Wawona Packing Company has issued a voluntary recall on the stone fruit it distributes due to a possible Listeria outbreak. Video provided by Newsy
Powered by NewsLook.com
Huge Schizophrenia Study Finds Dozens Of New Genetic Causes

Huge Schizophrenia Study Finds Dozens Of New Genetic Causes

Newsy (July 22, 2014) The 83 new genetic markers could open dozens of new avenues for schizophrenia treatment research. Video provided by Newsy
Powered by NewsLook.com
CDC Head Concerned About a Post-Antibiotic Era

CDC Head Concerned About a Post-Antibiotic Era

AP (July 22, 2014) Sounding alarms about the growing threat of antibiotic resistance, CDC Director Tom Frieden warned Tuesday if the global community does not confront the problem soon, the world will be living in a devastating post-antibiotic era. (July 22) Video provided by AP
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins