Navigation Links
Flexible neck in cell-receptor DC-SIGN targets more pathogens
Date:7/14/2009

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
kloeppel@illinois.edu
217-244-1073
University of Illinois at Urbana-Champaign
Source:Eurekalert

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:
*Name:
*Comment:
*Email:
(Date:4/28/2016)... -- First quarter 2016:   , Revenues ... first quarter of 2015 The gross margin was 49% ... and the operating margin was 40% (-13) Earnings per ... from operations was SEK 249.9 M (21.2) , Outlook ... 7,000-8,500 M. The operating margin for 2016 is estimated ...
(Date:4/15/2016)... DUBLIN , April 15, 2016 ... of the,  "Global Gait Biometrics Market 2016-2020,"  report ... http://photos.prnewswire.com/prnh/20160330/349511LOGO ) , ,The global gait ... CAGR of 13.98% during the period 2016-2020. ... movement angles, which can be used to compute ...
(Date:3/29/2016)... , March 29, 2016 ... "Company") LegacyXChange "LEGX" and SelectaDNA/CSI Protect are pleased to ... ink used in a variety of writing instruments, ensuring ... of originally created collectibles from athletes on LegacyXChange will ... analysis of the DNA. Bill Bollander ...
Breaking Biology News(10 mins):
(Date:5/25/2016)... Bangkok, Thailand (PRWEB) , ... May 25, 2016 ... ... the participation of a Thai delegation at BIO 2016 in San Francisco. Located ... private sector will be available to answer questions and discuss the Thai biotechnology ...
(Date:5/25/2016)... ... May 25, 2016 , ... WEDI, the nation’s leading authority on the use ... W. Stellar has been named by the WEDI Board of Directors as WEDI’s president ... executive leader with more than 35 years of experience in healthcare, association management and ...
(Date:5/24/2016)... La Jolla, CA (PRWEB) , ... May 24, 2016 , ... ... and financial planning for corporate executives and entrepreneurs, held The Future of San Diego ... leaders in the San Diego life science community attended the event with speakers Dr. ...
(Date:5/23/2016)... 23, 2016 Oxitec CEO Hadyn ... at 10:15 a.m. ET before the United States House Committee ... mosquitos can play in controlling the spread of the ... virus.      (Logo: http://photos.prnewswire.com/prnh/20150630/227348 ) ... a self-limiting gene. Trials in Brazil , ...
Breaking Biology Technology: