Biology subjects

Hessler, G.

Publications and source records attributed to Hessler, G..

4 recordsLinked to original sources

bioRxiv2026

Arabidopsis cysteine protease RD19 limits RBOHD-generated ROS production in pattern triggered immunity

Plants perceive pathogenic threats through receptors localized at the plasma membrane and inside cells to initiate pattern-triggered immunity (PTI) and effector-triggered immunity (ETI), respectively. PTI and ETI pathways are interconnected and partially converge on the EDS1-PAD4-ADR1 branch which stimulates anti-pathogen defence. Besides these canonical immune pathways, proteolysis plays a pivotal role in immunity by regulating the abundance and activities of diverse components. We previously identified Arabidopsis papain-like cysteine protease RD19 as a PAD4 interactor and showed that RD19 promotes resistance to host-adapted pathogens. Here, we investigated the contribution of RD19 to bacterial flg22 and nlp20 elicited PTI responses which exhibit, respectively, partial and high PAD4 dependence. We show that although PAD4 and RD19 both promote PTI, they have separate functions. In resting (non-triggered) and nlp20-triggered tissues, RD19 limits RBOHD protein accumulation and consequently ROS production. Using N-terminomic enrichment and protease cleavage site identification methods we identify candidate RD19 substrates in resting and nlp20-responding tissues. Our analysis shows that two immune-related aspartyl proteases AED3 and AED2/ASPG1 are likely direct RD19 targets. This study reveals a role of RD19 in ROS regulation and advances our understanding of proteolysis and dynamic RD19 substrate targeting in plant immunity.

plant biology↗

bioRxiv2023

Deep Batch Active Learning for Drug Discovery

A key challenge in drug discovery is to optimize, in silico, various absorption and affinity properties of small molecules. One strategy that was proposed for such optimization process is active learning. In active learning molecules are selected for testing based on their likelihood of improving model performance. To enable the use of active learning with advanced neural network models we developed two novel active learning batch selection methods. These methods were tested on several public datasets for different optimization goals and with different sizes. We have also curated new affinity datasets that provide chronological information on state-of-the-art experimental strategy. As we show, for all datasets the new active learning methods greatly improved on existing and current batch selection methods leading to significant potential saving in the number of experiments needed to reach the same model performance. Our methods are general and can be used with any package including the popular DeepChem library.

bioinformatics↗

bioRxiv2022

TIR-catalyzed ADP-ribosylation reactions produce signaling molecules for plant immunity

Plant pathogen-activated immune signaling by nucleotide-binding leucine-rich repeat (NLR) receptors with an N-terminal Toll/Interleukin-1 receptor (TIR) domain converges on Enhanced Disease Susceptibility 1 (EDS1) and its direct partners Phytoalexin Deficient 4 (PAD4) or Senescence-Associated Gene 101 (SAG101). TIR-encoded NADases produce signaling molecules to promote exclusive EDS1-PAD4 and EDS1-SAG101 interactions with helper NLR sub-classes. Here we show that TIR-containing proteins catalyze adenosine diphosphate (ADP)-ribosylation of adenosine triphosphate (ATP) and ADP ribose (ADPR) via ADPR polymerase-like and NADase activity, forming ADP-ribosylated ATP (ADPr-ATP) and ADPr-ADPR (di-ADPR), respectively. Specific binding of di-ADPR or ADPr-ATP allosterically promotes EDS1-SAG101 interaction with helper NLR N requirement gene 1A (NRG1A) in vitro and in planta. Our data reveal an enzymatic activity of TIRs that enables specific activation of the EDS1-SAG101-NRG1 immunity branch.

plant biology↗

bioRxiv2022

Identification and receptor mechanism of TIR-catalyzed small molecules in plant immunity

Plant nucleotide-binding leucine-rich-repeat receptors (NLRs) with an N-terminal toll/interleukin-1 receptor (TIR) domain sense pathogen effectors to enable TIR-encoded NADase activity for immune signaling. TIR-NLR (TNL) signaling requires conserved helper NLRs NRG1 and ADR1 and the lipase-like protein EDS1 that functions as a heterodimer with each of its paralogs PAD4 and SAG101. We show that TIR-containing proteins catalyze production of 2-(5-phosphoribosyl)-5-adenosine mono-/di-phosphate (pRib-AMP/ADP) in vitro and in planta. Biochemical and structural data demonstrate that EDS1-PAD4 is a receptor complex for pRib-AMP/ADP. pRib-ADP binding triggers a conformational change in the PAD4 C-terminal domain to allosterically promote EDS1-PAD4 interaction with ADR1-L1 but not NRG1A. Our study identifies TIR-catalyzed pRib-AMP/ADP as a missing link in TIR signaling via EDS1-PAD4 and as likely second messengers for plant immunity.

plant biology↗