Chemical biology news from across RSC Publishing.
Instant insight: Beryllium: friend or foe?
16 July 2008
Brian Scott and colleagues at Los Alamos National Laboratory, US, examine the molecular basis of chronic beryllium disease
Beryllium pervades today's technologies, from cars and computers through to dental prosthetics. Its popularity is related to its unique properties: it is lightweight, six times stiffer than steel, has a high melting point (1285 ēC) and heat absorption capacity, and is non-magnetic and corrosion resistant. Beryllium also reflects neutrons and is used for nuclear power and weapons applications. In the year 2000 the US used 390 tons of beryllium, with an estimated value of $140 million.
A beryllium antigen (centre) binds to an HLA molecule on an antigen presenting cell and is presented to a T cell, triggering an immune response
It is thought that the immune response to beryllium is triggered when the unwittingly-inhaled element is detected by antigen presenting cells (APC, see figure). An unknown beryllium species serves as the antigen which binds to a human leukocyte antigen (HLA) molecule on an APC's surface. The beryllium antigen is then presented to a T cell - a white blood cell with a key role in immune response. Research over the past six years at Los Alamos has resulted in a more complete picture of beryllium's speciation under biological conditions, including its interactions with proteins and the subsequent immunological consequences.
Through the study of several biologically relevant small molecule complexes of beryllium, it was discovered that beryllium has a high propensity to displace hydrogen atoms in strong hydrogen bonds. These bonds, often formed between amino acids containing carboxylate and alcohol groups, help provide the framework supporting protein structure and function. Extending this model to real biological systems, it was shown that beryllium displaced all 12 strong hydrogen bond atoms in transferrin, an iron transport protein found in blood plasma. This presents a potential pathway for beryllium to enter cells with transferrin receptors. These binding studies represent a new paradigm for beryllium binding in biological systems.
Related to its propensity to displace hydrogen bond atoms, beryllium is known to form polymetallic clusters with carboxylate groups. So it has been predicted that beryllium will also form clusters in proteins with many adjacent carboxylate residues. A striking discovery was that the HLA molecules of CBD patients contain a larger number of carboxylate residues than the HLA molecules of people without CBD. And 9Be NMR binding studies point to a carboxylate bridged cluster of beryllium atoms as an integral structural feature of the antigen (see figure).
A multidisciplinary, molecular based approach to studying CBD has identified relevant beryllium species, their interactions with proteins and the potential roles they play in disease. This may not only lead to potential cures and therapeutics for CBD, but also lend insight into mechanisms of other metal and autoimmune diseases.
Read more in the feature article 'The bioinorganic chemistry and associated immunology of chronic beryllium disease' in ChemComm
Link to journal article
The bioinorganic chemistry and associated immunology of chronic beryllium disease
Brian L. Scott, T. Mark McCleskey, Anu Chaudhary, Elizabeth Hong-Geller and S. Gnanakaran, Chem. Commun., 2008, 2837
Also of interest
Exposure to beryllium and its effect on human health is of increasing concern. Issue 6, 2006 of JEM features several papers on this important area.
Mike J Brisson
This comprehensive book describes all aspects of the current sampling and analysis techniques for trace-level beryllium in the workplace.