Metals and proteins are crucial partners in keeping organisms healthy and stable. And yet the extent to which this molecular metalloprotein team works at the cellular level is not known because the numbers, amounts and types of metal-containing proteins in any organism have remained something of a mystery.

Now, in a study led by a researcher at the University of Georgia a team of scientists has shown through an entirely new method that these so-called metalloproteins are much more diverse and extensive than previously recognised and that it is now possible to determine all the metals in an organism in one fell swoop through a reliable, genome-wide approach.

"Metalloproteins play key roles in most biological processes, including respiration, photosynthesis and drug metabolism," said Michael W. Adams, Distinguished Research Professor in the department of biochemistry and molecular biology at UGA and lead author on the new research. "But predicting from a genome sequence the numbers and types of metals an organism assimilates from its environment or needs to function has been impossible for a number of reasons."

The new method, which combines liquid chromatography, high-throughput tandem mass spectometry and inductively coupled plasma mass spectometry, reveals all the metalloproteins in an organism—and what the team found has been very surprising, since metals now seem to be much more important for proteins than ever before suspected. Knowledge about how metals work in proteins has given insights into such things as how proteins repair DNA damaged by cancer-causing processes, how organisms get energy for growth and how some biofuels are produced. The importance of the work may therefore go in many diverse directions and promises to lead to important discoveries and applications in many biological fields, Adams said.

One of the major surprises of the study is the sheer number of proteins in microbial metalloproteomes that remain uncharacterised. (A metalloproteome is the complete number of metal-containing proteins in any individual organism.) This means that the role of metals in proteins, already known to be important, extends considerably beyond what science currently knows.

Since the team is now involved in automating and miniaturising the steps in the method, it is entirely possible that dramatic and as yet unknown roles for metals in organisms may soon be discovered. And that could lead to such things as new drugs that might correct the mis-incorporation of metals into cells that potentially can lead to diseases or disorders as well as new diagnostic methods for detecting diseases and in determining the toxic effects of heavy metals.

University of Georgia