Metalloproteomics: challenges and prospective for clinical research applications

Abstract

Metals are essential cofactors, utilized in many critical cellular processes. For example, zinc is important in insulin biosynthesis and may play a role in Alzheimer's disease, but much of how the zinc-mediated process remains unknown. Knowing which metal is in which protein at a given point in time would lead to new insights into how metals work in biological systems. New tools are being developed to investigate the biochemistry and cell biology of metals, with potential for biomedical applications. In this report, we consider the promise and limitations of metalloproteins detection techniques. We provide a brief overview of the techniques available and a discussion of the technical challenges to biomedical applications, with particular focus on what must be overcome for the potential of these approaches to be achieved.

Keywords::

• elemental analysis
• metalloproteins
• metalloproteomics
• metals
• molecular pathology

Financial & competing interests disclosure

This work was supported by the Department of Energy, Office of Science Contract DE-AC-02-06CH11357. The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.

Key issues

• An intricate network of protein interactions ensures that metals are in the right locations, at the right time and in the right amount for human health.

• Over the past few decades, imaging has become an increasingly powerful tool, and the direct approaches it enables have shed new light on the biology of metals.

• There is an imminent need for tools that relate new images of metal ion homeostasis to the proteins responsible for changing it.

• Some tools have emerged, combining separations techniques such as electrophoresis and liquid chromatography with detection techniques such as mass spectrometry, X-ray fluorescence and autoradiography.

• It remains a challenge to work with biomedical samples, but the payoff is great, and the field is rapidly evolving.

Notes