Protein study shows evolutionary link between plants, humans

February 15, 2010

WEST LAFAYETTE, Ind. - Inserting a human protein important in cancer development was able to revive dying plants, showing an evolutionary link between plants and humans and possibly making it easier to study the protein's function in cancer development, a Purdue University study has shown.

The aminopeptidase M1 protein, or APM1, is critical for root development in plants. Arabidopsis plants lacking the protein will die, but can be rescued if the protein is restored.

During experiments, Wendy Peer, a research assistant professor of horticulture, found that inserting a similar protein found in humans, called insulin responsive aminopeptidase, or IRAP, also rescued the plants.

"APM1 and IRAP are in the same group," said Peer, whose results were published in the early online version of the journal Plant Physiology. "M1 aminopeptidase activity is such a fundamental process that it's been conserved evolutionarily. This protein has changed very little over time."

Peer said the finding could advance the understanding of this class of proteins because it might make it possible to conduct studies with plants instead of animals, offering researchers more control and options. Humans with altered function of the equivalent proteins often have leukemia or other cancers.

"There are more tools available in Arabidopsis to study this class of proteins than are available in animals," Peer said. "This research could be translational and helpful in the animal field or with human health. If humans have changes in these peptidases, they're very sick. Understanding how these proteins work in plants will help us understand how they work in humans."

APM1's function isn't entirely understood in plants. M1 aminopeptidases are thought to remove amino acids from proteins, thereby either activating or deactivating those proteins. M1 aminopeptidases also break down accumulations of proteins related to Alzheimer's disease.

"APM1 can alter the function of other proteins with its activity," Peer said.

Peer wants to understand which proteins APM1 targets and how it changes those proteins, thereby affecting changes in a plant's development. She is working to discover which amino acids in APM1 are necessary for it to function.

Peer and Angus Murphy, a Purdue professor of horticulture, have been working on this problem for several years. They identified Arabidopsis mutants that were missing APM1 and inserted modified APM1 proteins missing particular amino acids into the mutants to determine whether the modified APM1 protein could rescue the seedlings.

The next step in Peer's research is to determine APM1's target protein to better understand why APM1 is important for root growth. The National Science Foundation funded the research.

Writer: Brian Wallheimer, 765-496-2050, 

Source: Wendy Peer, 765-496-7958,

Ag Communications: (765) 494-8415;
Steve Leer,
Agriculture News Page



Catalytic and Protein-Protection Interaction Domains
Are Required for APM1 Function

Fazeeda N. Hosein, Anindita Bandyopadhyay,
Wendy Ann Peer, Angus S. Murphy

The M1 metallopeptidase APM1 is essential for embryonic, vegetative, and reproductive development in Arabidopsis. Here we show that, like mammalian M1 proteases, APM1 appears to have distinct enzymatic and protein-protein interaction domains and functions as a homodimer. Arabidopsis seedlings treated with ezetimibe, an inhibitor of M1 protein-protein interactions, mimicked a subset of apm1 phenotypes distinct from those resulting from treatment with PAQ-22, an inhibitor of M1 catalytic activity, suggesting that the APM1 catalytic and interaction domains can function independently. apm1-1 knockdown mutants transformed with catalytically inactive APM1 did not prevent seedling lethality. However, apm1-2 has a functional enzymatic domain but lacks the C-terminus, and transformation with catalytically inactive APM1 rescued the mutant. Overexpression of human IRAP rescued all apm1 phenotypes, suggesting that the catalytic activity was sufficient to compensate for loss of APM1 function, while overexpression of catalytically inactive IRAP only rescued apm1-2. Increased catalytic activity alone is not sufficient to compensate for loss-of-APM1-function, as overexpression of another Arabidopsis M1 family member lacking an extended C-terminus did not rescue apm1-1. The protein interactions facilitating enzymatic activity appear to be dependent on the C-terminus of APM1, as transformation with an open reading frame containing an internal deletion of a portion of the C-terminus or a point mutation in a dileucine motif did not rescue the mutant. These results suggest that both the catalytic and interaction domains are necessary for APM1 function, but that APM1 function and oligomerization does not require the domains to be present in the same linear molecule.