Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Researchers reveal crucial immune fighter role of the STING protein

19.06.2012
Key protein's double wing-like crystal structure captures secreted molecules from invading pathogens, activating the body's powerful immune response

Researchers at Weill Cornell Medical College have unlocked the structure of a key protein that, when sensing certain viruses and bacteria, triggers the body's immediate immune response.

In the journal Molecular Cell, scientists describe the double wing-like crystal structure of this key protein, known as STING, which is a soldier on the front-line of the body's defense against pathogens. Researchers also show STING in action, displaying evidence of a bacterial infection -- an action that launches the body's innate immune response.

"Activation of STING is crucial to the ability of the human body to pick out bits of molecules secreted by pathogens, including many different viruses and bacteria, and alert the human body that they are there. By solving the structure of this protein, we now know how they do this crucial task," says the study's lead author, Dr. Qian Yin, a postdoctoral associate in the laboratory of Dr. Hao Wu, professor of Biochemistry at Weill Cornell Medical College.

"The STING structure provides a remarkable example of the pathogen-host interactions in which a unique microbial molecule directly engages the innate immune system," says Dr. Wu, the study's senior investigator and director of the Lab of Cell Signaling at Weill Cornell.

While the findings have no immediate clinical significance, they might be useful in helping to make vaccines against pathogens more effective. "Based on the structure we have of STING interacting with molecules secreted from bacteria, we may be able to design new molecules that induce a stronger, more persistent immune response," says Dr. Yin.

STING's wings and tail respond to invaders

All plant and animal life use an innate immune response to recognize and respond to an assault by pathogens. This primitive response is immediate, but not long-lasting or protective; the secondary, adaptive immune response sets up the long-term defense.

Previously, scientists thought the innate response was generic, but recently, investigators uncovered proteins expressed by cells of the innate immune system that identify specific molecular patterns linked to microbial pathogens. STING was recently identified as a member of a family of proteins that is involved in this pattern recognition task. It is specifically tasked at finding viruses that have double-stranded DNA genomes, and with locating bacteria.

While STING does not confront viruses or viral molecules directly, with bacteria, STING is on the lookout for small molecules that bacteria use to communicate within their cellular bodies. These molecules are cyclic-di-GMP, produced by most bacteria, and cyclic-di-AMP, used by bacteria that grow inside the cells of a host.

However STING is activated, the end result is the same, Dr. Yin says. STING induces a response from interferon, which activates other immune cells that kill the invading parasites.

The crystal structure of STING developed by the research team explains the overall structure of the protein. The second structure of STING, bound to cyclic-di-GMP, explains how the protein can recognize and pick up both cyclic-di-GMP and cyclic-di-AMP. This and other published data suggests how STING activates an immune response.

Dr. Yin describes STING's structure as two wings, which form the bottom and sides that hold cyclic-di-GMP. "It is like two people holding out their left or right hands, wrists joining and palms facing each other, and holding something in their palms."

"The amazing thing is STING only binds to cyclic-di-GMP and, to a lesser degree, cyclic-di-AMP, leaving all other nucleotides in the human body quite safe -- meaning it is not picking up natural human molecules," she says. "To use the hands analogy again, only cyclic-di-GMP and cyclic-di-AMP can fit into the space between the two hands. Other nucleotides are too small and they will slip."

The researchers also propose that once STING's wings picks up cyclic-di-GMP, the molecule frees up the tail of STING's protein? which then engages with other proteins.

"We believe this movement of the tail section of the protein is the switch that turns on the interferon response," says Dr. Yin.

"This work has uncovered a number of unexpected insights into how STING works," says Dr. Wu. "By binding tightly only to tiny molecules produced by bacteria, which then turns on the interferon switch, it prevents the immune system from attacking the body's own cells."

Study co-authors include Dr. Yuan Tian and Dr. Venkataraman Kabaleeswaran from Weill Cornell Medical College; Dr. Xiaomo Jiang and Dr. Zhijian J. Chen from the University of Texas Southwestern Medical Center; and Dr. Daqi Tu and Dr. Michael J. Eck from Harvard Medical School.

Weill Cornell Medical College

Weill Cornell Medical College, Cornell University's medical school located in New York City, is committed to excellence in research, teaching, patient care and the advancement of the art and science of medicine, locally, nationally and globally. Physicians and scientists of Weill Cornell Medical College are engaged in cutting-edge research from bench to bedside, aimed at unlocking mysteries of the human body in health and sickness and toward developing new treatments and prevention strategies. In its commitment to global health and education, Weill Cornell has a strong presence in places such as Qatar, Tanzania, Haiti, Brazil, Austria and Turkey. Through the historic Weill Cornell Medical College in Qatar, the Medical College is the first in the U.S. to offer its M.D. degree overseas. Weill Cornell is the birthplace of many medical advances — including the development of the Pap test for cervical cancer, the synthesis of penicillin, the first successful embryo-biopsy pregnancy and birth in the U.S., the first clinical trial of gene therapy for Parkinson's disease, and most recently, the world's first successful use of deep brain stimulation to treat a minimally conscious brain-injured patient. Weill Cornell Medical College is affiliated with NewYork-Presbyterian Hospital, where its faculty provides comprehensive patient care at NewYork-Presbyterian Hospital/Weill Cornell Medical Center. The Medical College is also affiliated with the Methodist Hospital in Houston.

Lauren Woods | EurekAlert!
Further information:
http://www.weill.cornell.edu

More articles from Life Sciences:

nachricht Unique genome architectures after fertilisation in single-cell embryos
30.03.2017 | IMBA - Institut für Molekulare Biotechnologie der Österreichischen Akademie der Wissenschaften GmbH

nachricht Transport of molecular motors into cilia
28.03.2017 | Aarhus University

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: A Challenging European Research Project to Develop New Tiny Microscopes

The Institute of Semiconductor Technology and the Institute of Physical and Theoretical Chemistry, both members of the Laboratory for Emerging Nanometrology (LENA), at Technische Universität Braunschweig are partners in a new European research project entitled ChipScope, which aims to develop a completely new and extremely small optical microscope capable of observing the interior of living cells in real time. A consortium of 7 partners from 5 countries will tackle this issue with very ambitious objectives during a four-year research program.

To demonstrate the usefulness of this new scientific tool, at the end of the project the developed chip-sized microscope will be used to observe in real-time...

Im Focus: Giant Magnetic Fields in the Universe

Astronomers from Bonn and Tautenburg in Thuringia (Germany) used the 100-m radio telescope at Effelsberg to observe several galaxy clusters. At the edges of these large accumulations of dark matter, stellar systems (galaxies), hot gas, and charged particles, they found magnetic fields that are exceptionally ordered over distances of many million light years. This makes them the most extended magnetic fields in the universe known so far.

The results will be published on March 22 in the journal „Astronomy & Astrophysics“.

Galaxy clusters are the largest gravitationally bound structures in the universe. With a typical extent of about 10 million light years, i.e. 100 times the...

Im Focus: Tracing down linear ubiquitination

Researchers at the Goethe University Frankfurt, together with partners from the University of Tübingen in Germany and Queen Mary University as well as Francis Crick Institute from London (UK) have developed a novel technology to decipher the secret ubiquitin code.

Ubiquitin is a small protein that can be linked to other cellular proteins, thereby controlling and modulating their functions. The attachment occurs in many...

Im Focus: Perovskite edges can be tuned for optoelectronic performance

Layered 2D material improves efficiency for solar cells and LEDs

In the eternal search for next generation high-efficiency solar cells and LEDs, scientists at Los Alamos National Laboratory and their partners are creating...

Im Focus: Polymer-coated silicon nanosheets as alternative to graphene: A perfect team for nanoelectronics

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are less stable. Now researchers at the Technical University of Munich (TUM) have, for the first time ever, produced a composite material combining silicon nanosheets and a polymer that is both UV-resistant and easy to process. This brings the scientists a significant step closer to industrial applications like flexible displays and photosensors.

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

International Land Use Symposium ILUS 2017: Call for Abstracts and Registration open

20.03.2017 | Event News

CONNECT 2017: International congress on connective tissue

14.03.2017 | Event News

ICTM Conference: Turbine Construction between Big Data and Additive Manufacturing

07.03.2017 | Event News

 
Latest News

'On-off switch' brings researchers a step closer to potential HIV vaccine

30.03.2017 | Health and Medicine

Penn studies find promise for innovations in liquid biopsies

30.03.2017 | Health and Medicine

An LED-based device for imaging radiation induced skin damage

30.03.2017 | Medical Engineering

VideoLinks
B2B-VideoLinks
More VideoLinks >>>