Functional and Systems Biology
What Connects Zinc to Proteins in Cells
Unraveling how micronutrient zinc binds with proteins in cells to keep plants and animals healthy
Scientists have discovered how zinc reaches the proteins that need it. As shown in this artist's rendering, a protein (pink) delivers zinc (the white pearl) to bind with proteins within the cell. (Image courtesy of Crysten E. Blaby-Haas)
The Science
It is well known that zinc is an important metal that works with proteins to help regulate the health of plants and animals, including humans. But scientists haven’t been able to tease out how zinc gets to the right proteins. While some think a particular enzyme makes the connection between zinc and the various proteins, others think that there might be something inside the proteins themselves that pull in and bind the metal. By digging deep into the genetics of some of the zinc-dependent proteins, a team of scientists have now identified the physical interactions that link proteins and zinc in humans and fungi. As a result, the latest theory is that a particular type of protein labeled COG0523 serves as a chaperone for ushering zinc to the proteins that need it.
The Impact
Zinc deficiency in the human diet is a serious problem around the world. Plants deficient in the metal are smaller and yield food with poor zinc nutritional value. Zinc deficiency in humans can cause stunted growth, compromised immunity, and neurological defects. The metal is also a key micronutrient in hidden hunger where a lack of sufficient vitamins and minerals is estimated to affect 2 billion people worldwide. Understanding how plants and animals take up and process zinc has become an important challenge for keeping plants and animals healthy.
Summary
A multi-institutional team of scientists compared interactions among genes and molecules found in specific types of cells to generate a potential list of proteins that might involve the use of zinc. They swiftly narrowed in on the COG0523 family, a large and diverse group of proteins. Using advanced analysis techniques, including isobaric mass tag quantitation and mass spectrometry available from EMSL, the Environmental Molecular Sciences Laboratory, a Department of Energy (DOE) User Facility, they studied proteins in living cells from humans and two fungi. The team discovered that some proteins act as chaperones, delivering zinc to important enzymes in the cell. Loss of zinc led to complex impacts on protein functioning, which became worse when the chaperone was deleted. These findings will help scientists pinpoint how zinc is bound and moves through cells. Moreover, they will also help scientists understand how zinc moves through the environment because as carbon dioxide levels rise, the overall movement of zinc through the environment decreases.
Contacts
Crysten E. Blaby-Haas, Lawrence Berkeley National Laboratory, cblaby@lbl.gov
Kim Hixson, Environmental Molecular Sciences Laboratory, kim.hixson@pnnl.gov
Mary Lipton, Environmental Molecular Sciences Laboratory, mary.lipton@pnnl.gov
Carrie Nicora, Pacific Northwest National Laboratory, carrie.nicora@pnnl.gov
Funding
This work was supported by the DOE Office of Science, Biological and Environmental Research program, as part of the Quantitative Plant Science Initiative Special Focus Area at Brookhaven National Laboratory. Scientists conducted tandem mass tagging-proteomics research at EMSL, the Environmental Molecular Sciences Laboratory, a DOE Office of Science User Facility. Additional work was conducted by the DOE Joint Genome Institute, another DOE Office of Science User Facility.
Publications
M. Pasquini, et al., “Zng1 is a GTP-dependent zinc transferase needed for activation of methionine aminopeptidase.” Cell Reports 39, 110834 (2022). [DOI: 10.1016/j.celrep.2022.110834]