Navigation Links
Flexible neck in cell-receptor DC-SIGN targets more pathogens

CHAMPAIGN, Ill. Pathogen recognition is the foundation of the body's immune response and survival against infection. A small cell-receptor protein called DC-SIGN is part of the immune system, and recognizes certain pathogens, including those responsible for Ebola, Dengue fever and HIV. How the molecule binds to pathogens has been unclear.

New findings from a research team led by University of Illinois chemist Deborah Leckband show that flexibility in the region near the binding sites of DC-SIGN plays a significant role in pathogen targeting and binding.

"Our work focuses on how DC-SIGN recognizes HIV and other pathogens, and on what structural features enable it to bind very tightly to those pathogens," said Leckband, the Reid T. Milner Professor of Chemistry at the U. of I. "Once we begin to understand the molecular design rules that lead to this tight binding, we can begin to design inhibitors to block this interaction."

To study the binding behavior of DC-SIGN (Dendritic Cell-Specific Intercellular adhesion molecule-3-Grabbing Non-integrin), also known as CD209 (Cluster of Differentiation 209), the researchers used a device called a surface force apparatus.

The surface force apparatus measures the molecular forces between two surfaces as they are first brought together and then pulled apart. In the current work, the surfaces were cell receptor DC-SIGN and a target membrane decorated with carbohydrates to mimic a pathogen surface.

The forces were measured as a function of the distance between the two surfaces, which was measured with single-angstrom resolution (an angstrom is 1 10-billionth of a meter).

"Our force-distance measurements provided the first direct, dynamic evidence for flexibility in the neck of DC-SIGN, and its possible role in pathogen recognition and binding," said Leckband, corresponding author of a paper accepted for publication in the Proceedings of the National Academy of Sciences, and posted on the journal's Web site.

From their force-distance measurements the researchers determined DC-SIGN's neck length as 28 nanometers (a nanometer is 1 billionth of a meter), in agreement with hydrodynamic measurements and theoretical estimates by other researchers, which placed the neck length between 20 and 30 nanometers.

When the protein binds to a pathogen, binding sites on the cell receptor rearrange slightly, to adapt to the target surface and maximize the bond. This 5 nanometer conformational change is binding-induced, and made possible by a flexible linker in the neck, the researchers report.

"The protein neck region acts as a stiff, but flexible, rod that projects the molecule's binding sites away from the cell surface," Leckband said. "A rigid presentation of the binding sites at the end of the neck would restrict DC-SIGN to a few specific, spatial forms. Instead, the molecule's flexibility and adaptability allow it to recognize a much wider range of pathogens."


Contact: James E. Kloeppel
University of Illinois at Urbana-Champaign

Related biology news :

1. Flexible solar strips light up campus bus shelter
2. Generalist bacteria discovered in coastal waters may be more flexible than known before
3. e-Smart(R) Technologies, Inc., Announces Next Generation Superthin Polyimide Flexible Circuit Biometric Super Smart Card(TM) card, the i am(TM) Card.
4. IGERT fellows to design biodevices using flexible electronics
5. A quicker, cheaper SARS virus detector -- one easily customizable for other targets
6. Demonstration Targets Terrorism
7. Identifying mega-targets for high-yield plant breeding
8. UC Davis researchers find molecule that targets brain tumors
9. Modified gene targets cancer cells a thousand times more often than healthy cells
10. UQ research targets West Nile virus and dengue fever
11. New genes present drug targets for managing cholesterol and glucose levels
Post Your Comments:
(Date:11/9/2015)... Calif. , Nov. 9, 2015  Synaptics Inc. ... interface solutions, today announced broader entry into the automotive ... solutions that match the pace of consumer electronics human ... biometric sensors are ideal for the automotive industry and ... Europe , ...
(Date:10/29/2015)... Va. , Oct. 29, 2015 Daon, ... today that it has released a new version of ... customers in North America have ... IdentityX v4.0 also includes a FIDO UAF certified ... are already preparing to activate FIDO features. These customers ...
(Date:10/27/2015)... -- In the present market scenario, security is one ... verticals such as banking, healthcare, defense, electronic gadgets, and ... secure & simplified access control and growing rate of ... bank accounts, misuse of users, , and so on. ... and smartphones are expected to provide potential opportunities for ...
Breaking Biology News(10 mins):
(Date:11/24/2015)... -- Clintrax Global, Inc., a worldwide provider of clinical research services headquartered ... the company has set a new quarterly earnings record in Q3 ... posted for Q3 of 2014 to Q3 of 2015.   ... , with the establishment of an Asia-Pacific ... United Kingdom and Mexico , with ...
(Date:11/24/2015)... ... November 24, 2015 , ... This fall, global software solutions leader SAP ... states to develop and pitch their BIG ideas to improve health and wellness in ... for votes to win the title of SAP's Teen Innovator, an all-expenses paid trip ...
(Date:11/24/2015)... , November 24, 2015 SHPG ) announced ... in the Piper Jaffray 27 th Annual Healthcare Conference in ... 1, 2015, at 8:30 a.m. EST (1:30 p.m. GMT). --> ... Financial Officer, will participate in the Piper Jaffray 27 th ... NY on Tuesday, December 1, 2015, at 8:30 a.m. EST (1:30 ...
(Date:11/24/2015)... , Nov. 24, 2015  Tikcro Technologies Ltd. (OTCQB: TIKRF) today ... December 29, 2015 at 11:00 a.m. Israel time, ... Tower, 98 Yigal Allon Street, 36 th Floor, Tel ... Eric Paneth and Izhak Tamir to the Board ... Skaliter as external directors; , approval of an amendment to certain ...
Breaking Biology Technology: