The function follows the form in plant immunity

Researchers at the Max Planck Institute for Plant Research (MPIPZ) and the University of Cologne in Germany have discovered a new biochemical mechanism that explains how immune proteins protect plants against invading microorganisms. Their findings are published in the journal cell.

We humans rely on our immune system to protect us from diseases caused by harmful microorganisms. Similarly, plants also produce immune responses when invaded by harmful microbes. Key players in these plant immune responses are the so-called immune receptors, which detect the presence of molecules supplied by foreign microorganisms and trigger protective reactions to repel invaders.

A subset of these immune receptors contains specialized regions known as toll-interleukin-1 receptor domains (TIRs) and function as enzymes, special proteins that break down the nicotinamide molecule adenine dinucleotide (NAD).⁺), a very common, multifunctional small molecule found in all living cells. Breakdown of NAD⁺, in turn, activates additional immune proteins, ultimately ending in the so-called “hypersensitive response”, a defense mechanism that leads to the death of plant cells at sites of infection as an effective way to protect the plant as a whole. However, studies show that the breakdown of NAD⁺although essential, it is not sufficient for plant protection, which implies that additional mechanisms need to be included.

Authors led by the respective authors, Jijie Chai, who is affiliated with MPIPZ, University of Cologne and Tsinghua University in Beijing, China, Paul Schulze-Lefert of MPIPZ and Bin Wu of the School of Biological Sciences, Nanyang University of Technology, Singapore, explores the function of TIR proteins and may indicate that these receptors not only degrade NAD⁺but intriguingly have an additional function – TIR domains also process molecules with phosphodiester bonds, usually found in RNA and DNA, which are present in cells mainly as large, linear single-stranded or double-stranded molecules.

Using structural analysis, the authors could show that TIR proteins form different multi-protein structures to degrade NAD⁺ or RNA / DNA, explaining how the same protein can play two roles. To cleave RNA / DNA molecules, TIR proteins follow the contours of RNA / DNA strands and wrap tightly around them like string beads. The ability of TIR proteins to form two alternative molecular complexes is characteristic of the whole family of immune receptors. Thus, the exact form of TIR proteins dictates the corresponding enzyme activity.

The authors went on to show that this function alone is not sufficient for cell death, suggesting that specific small molecules generated by the breakdown of RNA and DNA are responsible. Using analytical chemistry, scientists could identify molecules such as cAMP / cGMP (cyclic adenosine monophosphate / cyclic guanosine monophosphate), the so-called cyclic nucleotides that are present in all kingdoms of life. Interestingly, instead of the well-characterized 3 ′, 5′-cAMP / cGMP, the authors’ analysis showed that TIR domains trigger the production of so-called non-canonical 2 ′, 3′-cAMP / cGMP, mysterious “cousins” whose exact roles have not been clear. When they reduce TIR-mediated production to 2 ′, 3′-cAMP / cGMP, cell death activity is impaired, indicating that 2 ′, 3′-cAMP / cGMP molecules are important for plant immune responses.

If 2 ′, 3′-cAMP / cGMP promotes cell death in plants in response to infection, then it is prudent to keep their levels strictly under control. In fact, the authors found that a known negative regulator of TIR function in plants, NUDT7, acts by depleting 2 ′, 3′-cAMP / cGMP. Such negative regulators are released by certain pathogens during infection in plant cells, and scientists could show that these pathogenic proteins also deplete 2 ′, 3′-cAMP / cGMP. This suggests that invading microorganisms have developed clever strategies to disarm the 2 ′, 3′-cAMP / cGMP-dependent plant defense mechanism in their own favor.

Dongli Yu, one of the three co-authors of this study, along with Wen Song and Eddie Yong Jun Tan, summarized the importance of his study as follows: “We identified a new role for the TIR domain of immune receptors in protecting plants against infection. Looking ahead, identifying and characterizing the goals of 2 ′, 3′-cAMP / cGMP will propose new strategies to increase plant resistance to harmful microbes and thus contribute to food security. ”