Copper "Chaperone" Escorts Hazardous Heavy Metal In Cells

October 30, 1997

Heavy metal ions, which are toxic to cells, are nevertheless required in tiny amounts in a few key components of the cell's biochemical machinery. A team of scientists has now shown that a special "chaperone" protein encases one of these hazardous materials, copper, to safely escort it through the interior of the cell and deliver it to the specific site where it is needed. The existence of the copper chaperone suggests that other essential metals, such as zinc and iron, may have their own chaperones that function similarly.

The finding is reported in the Oct. 31 issue of the journal Science and is discussed in an accompanying editorial.

Researchers at Northwestern University, Johns Hopkins University and the University of Michigan showed that the copper chaperone protein, which floats freely inside the cell, picks up copper in its most highly reactive chemical state from a "pump" protein that is embedded in the cell's wall. The chaperone then transports this important but dangerous cargo to a few enzymes that use it to catalyze vital biochemical reactions.

"The cell needs copper and a few other heavy metals for essential enzymes, but when they're not in an enzyme's active site they can destroy cellular components," said Thomas O'Halloran, professor of chemistry at Northwestern and one of three senior authors on the paper.

The human body contains only five thousandths of an ounce of copper; a penny (which is actually 97.5 percent zinc) weighs 17 times as much.

The copper chaperone provides clues to the toxic mechanisms of other metals, such as silver and mercury, and also to two rare fatal diseases of copper metabolism, Wilson disease and Menkes' disease. These hereditary diseases each occur roughly once in every 30,000 births.

The researchers studied the copper chaperone protein from yeast, which provides a good model of copper metabolism in animal cells. They cloned the gene and put it into bacteria, which made large quantities of the protein for physical study. The human copper chaperones (there are known to be more than one) are required to transport copper, but diseases related to their malfunction have not yet been identified. The protein that malfunctions in Wilson and Menkes' diseases normally receives copper from a copper chaperone and has a very similar design to it, O'Halloran said.

Wilson and Menkes' diseases are not probably not the only disorders of copper metabolism. Another protein very similar to the copper chaperone is believed to carry copper to an enzyme called superoxide dismutase, or SOD, a primary antioxidant in the cell. Some researchers think that disorders in copper metabolism or in SOD itself play a role in the neurodegenerative disease ALS, or Lou Gehrig's disease.

Studying the function of the copper chaperone also should help scientists understand how other toxic metals are handled within the cell, O'Halloran said. "Mercury and silver are not essential to yeast or humans and therefore not likely to have chaperones," O'Halloran said. "But they might piggyback on the other metals' chaperones and wreak havoc on the cell."

Geneticist Valeria Culotta and her co-workers at Johns Hopkins SuJu Lin and Paul Schmidt cloned the copper chaperone protein gene in yeast and proved that the chaperone actually touches the protein to which it transfers the copper.

Spectroscopist James Penner-Hahn of the University of Michigan and his student Katrina Peariso used synchrotron radiation to probe the chemical state of copper within the chaperone protein. Robert Pufahl, Chris Singer and Christoph Fahrni worked with O'Halloran at Northwestern to isolate and characterize the chaperone protein molecule itself.

The research was supported by the National Institutes of Health.

Northwestern University

Related Protein Articles from Brightsurf:

The protein dress of a neuron
New method marks proteins and reveals the receptors in which neurons are dressed

Memory protein
When UC Santa Barbara materials scientist Omar Saleh and graduate student Ian Morgan sought to understand the mechanical behaviors of disordered proteins in the lab, they expected that after being stretched, one particular model protein would snap back instantaneously, like a rubber band.

Diets high in protein, particularly plant protein, linked to lower risk of death
Diets high in protein, particularly plant protein, are associated with a lower risk of death from any cause, finds an analysis of the latest evidence published by The BMJ today.

A new understanding of protein movement
A team of UD engineers has uncovered the role of surface diffusion in protein transport, which could aid biopharmaceutical processing.

A new biotinylation enzyme for analyzing protein-protein interactions
Proteins play roles by interacting with various other proteins. Therefore, interaction analysis is an indispensable technique for studying the function of proteins.

Substituting the next-best protein
Children born with Duchenne muscular dystrophy have a mutation in the X-chromosome gene that would normally code for dystrophin, a protein that provides structural integrity to skeletal muscles.

A direct protein-to-protein binding couples cell survival to cell proliferation
The regulators of apoptosis watch over cell replication and the decision to enter the cell cycle.

A protein that controls inflammation
A study by the research team of Prof. Geert van Loo (VIB-UGent Center for Inflammation Research) has unraveled a critical molecular mechanism behind autoimmune and inflammatory diseases such as rheumatoid arthritis, Crohn's disease, and psoriasis.

Resurrecting ancient protein partners reveals origin of protein regulation
After reconstructing the ancient forms of two cellular proteins, scientists discovered the earliest known instance of a complex form of protein regulation.

Sensing protein wellbeing
The folding state of the proteins in live cells often reflect the cell's general health.

Read More: Protein News and Protein Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.