Sialic shield: Immune insights from X-ray study

Skip to Navigation

Ezine

  • Published: Dec 1, 2014
  • Author: David Bradley
  • Channels: X-ray Spectrometry
thumbnail image: Sialic shield: Immune insights from X-ray study

Self recognition

Sialic acid structure generated using Chemspider. used X-ray crystallography and nuclear magnetic resonance (NMR) spectroscopy to identify the key determinants of a recognition process that relies chiefly on sialic acid, a glycan that is expressed on all human cells, to let the immune system distinguish between

An international team has used X-ray crystallography and nuclear magnetic resonance (NMR) spectroscopy to identify the key determinants of a recognition process that relies chiefly on sialic acid, a glycan that is expressed on all human cells, to let the immune system distinguish between "friend" and "foe". The findings could have important implications for immunology, vaccine research and understanding autoimmune disease.

The team comprises Bärbel Blaum and Thilo Stehle of the Interfaculty Institute of Biochemistry, University of Tübingen, Tübingen, Germany, Jonathan Hannan of the Department of Medicine, University of Colorado School of Medicine, Aurora, Colorado, USA, Andrew Herbert and Dušan Uhrín of The School of Chemistry, University of Edinburgh, Scotland, UK and David Kavanagh of the Institute of Genetic Medicine, International Centre for Life, Newcastle upon Tyne, UK. Stehle is also in the Department of Pediatrics, at Vanderbilt University School of Medicine, Nashville, Tennessee, USA.

Counter infection

To counter infection our immune systems must be able to distinguish friend from foe, our cells and proteins from pathogens In order to achieve this, the immune system utilizes characteristic molecular patterns displayed on the surface of each cell. One of these molecular patterns has now been identified in detail by the researchers who have identified the key determinants of a recognition process that relies chiefly on sialic acid, a glycan that is expressed on all human cells. Sialic acid is general name for any N- or O-substituted derivatives of neuraminic acid, a monosaccharide with a backbone containing nine carbon atoms. It does also specifically refer to the most common member of the group, N-acetylneuraminic acid.

Human cells are well known to be covered in complex glycans, long and branching chains of sugars. In terms of self recognition the sialic acid group - known to be involved in innate immune defence since the 1970s - is the most critical part of these glycans. Sialic acid underpins the complement system which comprises many proteins circulating in the blood stream which trigger the cascade of reactions that are aimed at destroying invaders. But, until now, researchers did not have a clear understanding of how sialic acid was able to block the complement system to prevent the defences from turning on the body's own cells.

Who goes there?

The researchers have now identified and crystallized a complex that forms the contact point between a healthy human cell and the complement system. Using NMR spectroscopy and X-ray studies, they solved the molecular structure of this complex revealing it to be composed of a glycan containing sialic acid and two domains of the complement system regulator, factor H. "On healthy human cells, the recognition of sialic acid by factor H stops the complement cascade short, so that cells with these sugar structures remain undamaged," explains team member Blaum.

There may be an immediate application for this finding in that the team suspects that in the rare, but serious, kidney disease atypical haemolytic-uraemic syndrome, aHUS, this recognition mechanism fails. "We know from genetic studies that a part of factor H is damaged in some aHUS patients, and it now turns out that this damage is often located in the sialic acid binding site in factor H," Blaum adds. The team believes that now that they have provided a better picture of the recognition process other researchers will be able to work towards a treatment for this condition. In the longer, term, the same insight could be used to treat infections where bacteria have hijacked factor H with its sialic acid to disguise themselves as human cells and so evade detection and destruction by the immune system.

Related Links

Nature Chem Biol 2014, online: "Structural basis for ​sialic acid-mediated self-recognition by ​complement factor H"

Article by David Bradley

The views represented in this article are solely those of the author and do not necessarily represent those of John Wiley and Sons, Ltd.

Social Links

Share This Links

Bookmark and Share

Microsites

Suppliers Selection
Societies Selection

Banner Ad

Click here to see
all job opportunities

Most Viewed

Copyright Information

Interested in separation science? Visit our sister site separationsNOW.com

Copyright © 2017 John Wiley & Sons, Inc. All Rights Reserved