Developments in imaging metal bound proteins and understanding role of metals in ‘Health and Disease’


Curated by: Dr. Venkat S Karra, Ph.D.

Metals are an environmental toxin and at the same time they also have therapeutic value, e.g., like the platinum in cisplatin that treats prostate cancer. Also metals such as copper, zinc, and iron are important nutrients -the special properties of these elements that make them useful to living organisms.

For example, copper deficiency alters the role of other cellular constituents involved in antioxidant activities. In both humans and animals, the major target organs for copper deficiency are the blood and hematopoietic system, the cardiovascular system, connective tissue and bone, the nervous system, and the immune system.

Therefore, proper management of these metals leads to ‘good health’ and at the same time the biological mismanagement of these metals leads to many diseases, including Lou Gehrig’s disease, Wilson and Menkes disease, and possibly even Alzheimer’s disease.

Alzheimer’s is an interesting one to study. The most recent study in understanding this disease is likely to give a ray of hope to many suffering with Alzheimer’s. This study was published in a recent issue of Neuron (Neuron, Volume 75, Issue 5, 824-837, 6 September 2012).

Authors of this publication have opened a new therapeutic door for Alzheimer’s research by shedding valuable light on the cell-signaling pathways of Aβ42, the form of Aβ-peptide most likely to clump into Alzheimer’s hallmark plaques. They discovered that deleting an enzyme known as JNK3 from the genes of mice with a model form of Alzheimer’s lowered Aβ-peptide production by 90 percent over the course of six months.

Now with over a third of all proteins thought to bind metals, knowing which metals are bound and how that binding changes in response to the environment will improve our understanding about health and disease and could help us restore sick by developing more targeted therapies.

Developing an approach for making determinations about the relationship of metals and proteins is complex, but scientists working at the U.S. Department of Energy Office of Science’s Advanced Photon Source (APS) at Argonne National Laboratory have made great strides in imaging metals within cells.

English: Advanced Photon Source, Argonne Natio...

English: Advanced Photon Source, Argonne National Laboratory. Nanoprobe. (Photo credit: Wikipedia)

Using the X-ray imaging capabilities afforded by the APS, researchers have seen, often for the first time, where the metals reside inside cells and tissues.

These capabilities have allowed researchers to see

– how the elemental content of bacteria change upon adhesion,

– fluxes of zinc in egg cells upon fertilization, and

– changes in the locations where copper is stored in a cell during the growth of blood vessels etc.

This work, which was featured in Metallomics, used X-ray fluorescence imaging (XRF) at X-ray Science Division (XSD) beamline 8-BM-B of the APS. The approach enabled the research team to identify a novel protein (PA5217) as a zinc-binding protein in P. aeruginosa. This finding highlights how this method not only determines changes in metal occupancy, but also identifies the associated protein.

This development possibly help researchers begin to identify which of the one-third of proteins that are thought to bind metals actually do.

This new technique help us understand as well the role of metals in ‘health and disease’ in general and plausibly that understanding could help us develop more targeted treatments.



Argonne National Laboratory


Comments RSS
  1. blood pressure

    You can definitely see your enthusiasm in the work you write. The world hopes for more passionate writers like you who aren’t afraid to say how they believe. At all times go after your heart.


  2. vskarra

    Thank You Dr. Shidhara, for your comments and all the comments are well taken. It is indeed an important step forward both in imaging technology as well as in understanding the patho-biology.


  3. Dr Shridhara K

    Good piece of information. Lot of research needs to be done to arrive at conclusions on the role of metals in cotrolling the diseases.


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