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Relationship: 3556

Title

A descriptive phrase which clearly defines the two KEs being considered and the sequential relationship between them (i.e., which is upstream, and which is downstream). More help

Binding to the QB site D1 protein leads to Decrease, Photosystem II efficiency

Upstream event

The causing Key Event (KE) in a Key Event Relationship (KER). More help

Binding to the QB site D1 protein

Downstream event

The responding Key Event (KE) in a Key Event Relationship (KER). More help

Decrease, Photosystem II efficiency

Key Event Relationship Overview

The utility of AOPs for regulatory application is defined, to a large extent, by the confidence and precision with which they facilitate extrapolation of data measured at low levels of biological organisation to predicted outcomes at higher levels of organisation and the extent to which they can link biological effect measurements to their specific causes.Within the AOP framework, the predictive relationships that facilitate extrapolation are represented by the KERs. Consequently, the overall WoE for an AOP is a reflection in part, of the level of confidence in the underlying series of KERs it encompasses. Therefore, describing the KERs in an AOP involves assembling and organising the types of information and evidence that defines the scientific basis for inferring the probable change in, or state of, a downstream KE from the known or measured state of an upstream KE. More help

AOPs Referencing Relationship

AOP Name	Adjacency	Weight of Evidence	Quantitative Understanding	Point of Contact	Author Status	OECD Status
Binding to plastoquinone B site leading to decreased population growth rate via photosystem II inhibition	adjacent	High	Low	Li Xie (send email)	Under development: Not open for comment. Do not cite

Taxonomic Applicability

Latin or common names of a species or broader taxonomic grouping (e.g., class, order, family) that help to define the biological applicability domain of the KER.In general, this will be dictated by the more restrictive of the two KEs being linked together by the KER. More help

Term	Scientific Term	Evidence	Link
Lemna minor	Lemna minor	High	NCBI
Chlamydomonas reinhardtii	Chlamydomonas reinhardtii	High	NCBI
Arabidopsis thaliana	Arabidopsis thaliana	High	NCBI

Sex Applicability

An indication of the the relevant sex for this KER. More help

Sex	Evidence
Unspecific	High

Life Stage Applicability

An indication of the the relevant life stage(s) for this KER. More help

Term	Evidence
All life stages	High

Key Event Relationship Description

Provides a concise overview of the information given below as well as addressing details that aren’t inherent in the description of the KEs themselves. More help

Binding of a stressor to the Q_B site of the D1 protein directly interferes with electron transfer within Photosystem II by blocking plastoquinone binding and reduction. This disruption slows or prevents electron flow from Q_A to Q_B, leading to impaired charge separation efficiency and increased recombination reactions. As a result, the functional efficiency of Photosystem II is reduced, which is commonly observed as decreases in parameters such as quantum yield and maximum photochemical efficiency.

Evidence Collection Strategy

Include a description of the approach for identification and assembly of the evidence base for the KER. For evidence identification, include, for example, a description of the sources and dates of information consulted including expert knowledge, databases searched and associated search terms/strings. Include also a description of study screening criteria and methodology, study quality assessment considerations, the data extraction strategy and links to any repositories/databases of relevant references.Tabular summaries and links to relevant supporting documentation are encouraged, wherever possible. More help

_{The literature was systematically filtered through a tiered process, where the AOP-helpFinder (v3.0) was applied to screening the initial candidate literature that related to the stressor-event and event-event relationships, followed by the Swift-Reviewer (Version 1.43.1063) to refine the corpus of evidence.}

Evidence Supporting this KER

Addresses the scientific evidence supporting KERs in an AOP setting the stage for overall assessment of the AOP. More help

The Key Event Relationship (KER) between binding at the Q_B site of the D1 protein and decreased Photosystem II (PSII) efficiency is strongly supported by structural, biochemical, and physiological evidence. Crystallographic analyses demonstrate that PSII-inhibiting herbicides bind specifically to the Q_B niche within the D1 protein, competitively blocking plastoquinone exchange and electron transfer from Q_A to Q_B (Broser et al., 2011). This disruption rapidly reduces photochemical efficiency, reflected by declines in Fv/Fm and impaired oxygen evolution (Maxwell & Johnson, 2000; Delieu & Walker, 1981). Mutational studies of D1 further confirm that alterations at the Q_B site modify herbicide sensitivity and PSII performance (Alfonso et al., 1996), establishing a direct mechanistic linkage.

Biological Plausibility

Addresses the biological rationale for a connection between KEupstream and KEdownstream. This field can also incorporate additional mechanistic details that help inform the relationship between KEs, this is useful when it is not practical/pragmatic to represent these details as separate KEs due to the difficulty or relative infrequency with which it is likely to be measured. More help

The biological plausibility of this key event relationship is high. The Q_Bbinding site of the D1 protein is a well-defined and essential component of Photosystem II, responsible for the binding and reduction of plastoquinone during photosynthetic electron transport (Lambreva et al., 2014; Velthuys, 1981). Binding of chemicals to this site is known to competitively inhibit plastoquinone exchange, thereby directly disrupting electron transfer from Q_A to Q_B (Battaglino et al., 2021; Zobnina et al., 2017). This mechanism leads to a rapid accumulation of reduced QA, increased charge recombination, and impaired stabilization of photochemical charge separation (Ermakova-Gerdes & Vermaas, 1998; Ohad & Hirschberg, 1992). Consequently, the efficiency of Photosystem II is reduced, which is consistently reflected by decreases in established photosynthetic performance metrics (Jansen et al., 1993). The direct structural and functional role of the Q_B site in electron transport provides a clear and mechanistically supported causal link between Q_B binding in the D1 protein and decreased Photosystem II efficiency (Nain-Perez et al., 2017; Zobnina et al., 2017).

Empirical Evidence

Provides specific (citable) evidence that supports the idea of a change in the upstream KE (KEupstream) leading to, or being associated with, a subsequent change in the downstream KE (KEdownstream), assuming the perturbation of KEupstream is sufficient. More help

The empirical support of this KER is considered high.

Rationale: A large body of experimental evidence demonstrates strong incidence, dose, and temporal concordance between chemical binding or interference at the Q_B site of the D1 protein and reduced Photosystem II (PSII) efficiency across cyanobacteria, algae, aquatic plants, and higher plants. These effects are consistently observed for well-characterized PSII inhibitors, with relatively few inconsistencies.

Evidence:

Dose concordance: In isolated pea thylakoid membranes, Q_B site herbicides with higher inferred Q_B affinity (diuron, terbuthylazine, metribuzin) inhibited PSII electron transfer and fluorescence-based PSII performance at substantially lower concentrations than lower-affinity inhibitors (e.g., bentazon, metobromuron). Reported I50 values were around 7–8 × 10⁻⁸M for diuron and 1–2 × 10⁻⁷M for terbuthylazine/metribuzin, derived from both DPIP photoreduction (PSII activity) and OJIP fluorescence (1–V_j, reflecting QA reduction and QB site interference) (Battaglino, Grinzato and Pagliano, 2021).

Incidence concordance: Direct inhibition of plastoquinone binding at the Q_B site leads to accumulation of reduced QA and impaired QA to QB electron transfer, which is consistently associated with reduced PSII efficiency in functional assays, including fluorescence-based measurements (Vermaas et al., 1984; Sundby et al., 1993; Broser et al., 2011).

Structural–functional concordance: Crystallographic and molecular studies have shown that PSII inhibitors bind within the QB_BB pocket of the D1 protein, physically blocking plastoquinone exchange. This structural interference provides direct mechanistic evidence linking QB_BB binding to impaired PSII electron transport and decreased PSII efficiency (Broser et al., 2011; Zimmermann et al., 2006).

Genetic concordance: Mutations in the D1 protein affecting the QB_BB region alter herbicide binding and are accompanied by changes in PSII electron transport efficiency and photochemical performance, supporting a causal relationship between perturbation at the QB_BB site and decreased PSII efficiency (Ohad and Hirschberg, 1992; Sundby et al., 1993).

Temporal concordance: In aquatic plants and seagrasses, inhibition of PSII efficiency occurs rapidly following exposure to PSII herbicides, while partial or full recovery of PSII function is observed after removal of the stressor, consistent with a direct and reversible inhibition of QB_BB-mediated electron transport (Macinnis-Ng and Ralph, 2003; Wilkinson et al., 2015).

Uncertainties and Inconsistencies

Addresses inconsistencies or uncertainties in the relationship including the identification of experimental details that may explain apparent deviations from the expected patterns of concordance. More help

Uncertainties remain regarding species-specific sensitivity and compensatory responses following Q_B-site binding. Structural evidence is strong in model organisms, but quantitative linkage between binding affinity and magnitude of PSII efficiency decline varies across taxa and exposure conditions. Additionally, secondary oxidative damage may confound the direct attribution solely to primary Q_B-site inhibition.

Known modulating factors

This table captures specific information on the MF, its properties, how it affects the KER and respective references.1.) What is the modulating factor? Name the factor for which solid evidence exists that it influences this KER. Examples: age, sex, genotype, diet 2.) Details of this modulating factor. Specify which features of this MF are relevant for this KER. Examples: a specific age range or a specific biological age (defined by...); a specific gene mutation or variant, a specific nutrient (deficit or surplus); a sex-specific homone; a certain threshold value (e.g. serum levels of a chemical above...) 3.) Description of how this modulating factor affects this KER. Describe the provable modification of the KER (also quantitatively, if known). Examples: increase or decrease of the magnitude of effect (by a factor of...); change of the time-course of the effect (onset delay by...); alteration of the probability of the effect; increase or decrease of the sensitivity of the downstream effect (by a factor of...) 4.) Provision of supporting scientific evidence for an effect of this MF on this KER. Give a list of references. More help

Modulating Factor (MF)	MF Specification	Effect(s) on the KER	Reference(s)
D1 protein genotype (psbA mutations)	Amino acid substitutions in the D1 protein affecting the Q_B binding niche (e.g. Ser264, Ser268 mutations)	Alters herbicide binding affinity at the QB site, leading to reduced or enhanced inhibition of QA→QB electron transfer and corresponding changes in the magnitude of PSII efficiency reduction	Ohad and Hirschberg (1992); Sundby et al. (1993); Alfonso et al. (1996); Oettmeier (1999)
Chemical binding affinity to QB	Structural differences among PSII inhibitors (e.g. diuron, atrazine, terbutryn, metribuzin) influencing QB site affinity	Higher QB binding affinity results in stronger and more rapid inhibition of PSII efficiency at lower concentrations, while lower-affinity compounds require higher doses	Tischer and Strotmann (1977); Fuerst and Michael (1991); Vermaas et al. (1984); Broser et al. (2011)
Photosystem II repair capacity	Ability to replace damaged D1 protein via de novo synthesis and PSII repair cycle	High repair capacity reduces duration and magnitude of PSII efficiency loss following QB site inhibition; limited repair capacity prolongs inhibition	Allakhverdiev et al. (2005); Wilhelm and Selmar (2011)
Species / taxonomic group	Cyanobacteria, algae, aquatic macrophytes, terrestrial plants	Sensitivity of PSII efficiency to QB-site inhibition varies among taxa due to differences in PSII structure, herbicide uptake, and repair dynamics	Broser et al. (2011); Wilkinson et al. (2015); Macinnis-Ng and Ralph (2003)
Exposure duration	Short-term pulse exposure versus sustained exposure	Short exposures often cause reversible PSII inhibition, while continuous exposure increases probability and magnitude of sustained PSII efficiency loss	Macinnis-Ng and Ralph (2003); Wilkinson et al. (2015)
Light intensity	High irradiance versus low or moderate light conditions	High light exacerbates PSII efficiency loss following QB site binding due to increased excitation pressure and photodamage; low light reduces severity of functional inhibition	Sundby et al. (1993); Wilhelm and Selmar (2011)

Quantitative Understanding of the Linkage

Captures information that helps to define how much change in the upstream KE, and/or for how long, is needed to elicit a detectable and defined change in the downstream KE. More help

The quantitative understanding of the linkage between Q_B-site binding in the D1 protein and decreased Photosystem II (PSII) efficiency is currently considered low. Although inhibition constants and structural binding interactions have been characterized for several PSII inhibitors (Broser et al., 2011), these molecular parameters are rarely quantitatively coupled with functional endpoints such as Fv/Fm decline or oxygen evolution rates (Maxwell & Johnson, 2000; Delieu & Walker, 1981). Most studies report concentration–response relationships at the whole-PSII level rather than linking fractional Q_B-site occupancy to photochemical impairment. Furthermore, species-specific repair capacity of the D1 protein and light-dependent damage processes introduce additional variability (Alfonso et al., 1996). Consequently, the mathematical response function necessary for qAOP parameterization remains insufficiently defined.

Response-response Relationship

Provides sources of data that define the response-response relationships between the KEs. More help

The response–response relationship between Q_B-site binding and decreased Photosystem II (PSII) efficiency remains insufficiently quantified. Empirically, increasing inhibitor concentration produces a sigmoidal decline in Fv/Fm and oxygen evolution rates (Maxwell & Johnson, 2000; Delieu & Walker, 1981). However, these functional responses are measured at the system level and are not directly parameterized against fractional Q_B-site occupancy (Broser et al., 2011). Variability in D1 turnover and photorepair dynamics further modifies the slope and threshold of the response curve (Alfonso et al., 1996), limiting precise quantitative extrapolation.

Time-scale

Information regarding the approximate time-scale of the changes in KEdownstream relative to changes in KEupstream (i.e., do effects on KEdownstream lag those on KEupstream by seconds, minutes, hours, or days?). More help

The time scale of this KER is rapid at the functional level. Q_B-site binding occurs within minutes of exposure, leading to immediate inhibition of electron transport and measurable declines in Fv/Fm and oxygen evolution (Delieu & Walker, 1981; Maxwell & Johnson, 2000). Longer-term effects depend on D1 repair dynamics and sustained exposure.

Known Feedforward/Feedback loops influencing this KER

Define whether there are known positive or negative feedback mechanisms involved and what is understood about their time-course and homeostatic limits. More help

Inhibition of electron transfer at the Q_B site promotes over-reduction of Q_A and enhances charge recombination, which increases reactive oxygen species (ROS) formation under illumination (Broser et al., 2011). Elevated ROS can further damage the D1 protein, reinforcing PSII impairment through a positive feedforward loop. Conversely, photosynthetic organisms possess a repair cycle involving proteolytic removal and resynthesis of damaged D1, partially restoring PSII efficiency (Alfonso et al., 1996). The balance between ROS-mediated damage and D1 repair capacity determines the persistence and magnitude of PSII inhibition under sustained exposure.

Domain of Applicability

A free-text section of the KER description that the developers can use to explain their rationale for the taxonomic, life stage, or sex applicability structured terms. More help

axonomic applicability: This KER applies to all oxygenic photosynthetic taxa possessing Photosystem II with a conserved D1 protein and functional Q_B binding site, including cyanobacteria, chlorophyte algae (e.g., Chlamydomonas reinhardtii), macrophytes (e.g., Lemna minor), and higher plants. The Q_B niche and its role in plastoquinone reduction are structurally conserved across these groups (Broser et al., 2011), supporting broad cross-taxon relevance.

Sex applicability: Not sex-specific. PSII structure and function are conserved in both male and female individuals of dioecious plants, and in clonal or unicellular species sex differentiation is not relevant.

Life-stage applicability: Applicable across all photosynthetically active life stages (e.g., vegetative cells, seedlings, mature leaves). Sensitivity may vary with developmental stage due to differences in D1 turnover, pigment composition, and photorepair capacity (Maxwell & Johnson, 2000), but the mechanistic linkage remains conserved.

Chemical Applicability: This KER is specifically applicable to chemicals that bind to the Q_B site of the D1 protein and inhibit plastoquinone exchange. It is strongly supported for classical PSII inhibitors, including triazines (e.g., atrazine), phenylureas (e.g., diuron), triazinones (e.g., metribuzin), and substituted ureas, which competitively occupy the Q_B niche and block electron transport (Broser et al., 2011; Alfonso et al., 1996). Applicability depends on structural compatibility with the hydrophobic Q_B binding pocket. Chemicals that impair photosynthesis via alternative mechanisms (e.g., PSI inhibitors, uncouplers, pigment synthesis inhibitors) fall outside this KER’s mechanistic domain, although they may produce similar downstream reductions in PSII efficiency through indirect pathways.

References

List of the literature that was cited for this KER description. More help

Alfonso, M., Pueyo, J.J., Gaddour, K., Etienne, A.-L., Kirilovsky, D., & Picorel, R. (1996). Induced new mutation of D1 serine-268 in soybean photosynthetic cell cultures produced atrazine resistance, increased stability of S2QB− and S3QB− states, and increased sensitivity to light stress. Plant Physiology, 112(4), 1499–1508.

Broser, M., Glöckner, C., Gabdulkhakov, A., Guskov, A., Buchta, J., Kern, J., Müh, F., Dau, H., Saenger, W., & Zouni, A. (2011). Structural basis of cyanobacterial photosystem II inhibition by the herbicide terbutryn. Journal of Biological Chemistry, 286(18), 15964–15972.

Battaglino, B., Grinzato, A., & Pagliano, C. (2021). Binding properties of photosynthetic herbicides with the QB site of the D1 protein in plant Photosystem II: A combined functional and molecular docking study. Plants, 10(8), 1501.

Delieu, T., & Walker, D.A. (1981). Polarographic measurement of photosynthetic oxygen evolution by leaf discs. New Phytologist, 89(2), 165–178.

Ermakova-Gerdes, S., & Vermaas, W. (1998). Mobility of the primary electron-accepting plastoquinone QA of Photosystem II in a Synechocystis sp. PCC 6803 strain carrying mutations in the D2 protein. Biochemistry, 37(17), 5918–5924.

Jansen, M. A. K., Depka, B., Trebst, A., & Edelman, M. (1993). Engagement of specific sites in the plastoquinone niche regulates degradation of the D1 protein in Photosystem II. Journal of Biological Chemistry, 268(1), 2470–2475.

Lambreva, M. D., Russo, D., Polticelli, F., & Rea, G. (2014). Structure/function/dynamics of Photosystem II plastoquinone binding sites. Current Protein & Peptide Science, 15(4), 332–345. https://doi.org/10.2174/1389203715666140327104802

Nain-Perez, A., Barbosa, L. C. A., Maltha, C. R. A., & Tavares, W. de S. (2017). Tailoring natural abenquines to inhibit the photosynthetic electron transport through interaction with the D1 protein in Photosystem II. Journal of Agricultural and Food Chemistry, 65(4), 782–791. https://doi.org/10.1021/acs.jafc.7b04624

Ohad, N., & Hirschberg, J. (1992). Mutations in the D1 subunit of Photosystem II distinguish between quinone and herbicide binding sites. The Plant Cell, 4(3), 273–282. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC160128/

Velthuys, B. R. (1981). Electron-dependent competition between plastoquinone and inhibitors for binding to Photosystem II. FEBS Letters, 126(2), 277–281. https://doi.org/10.1016/0014-5793(81)80260-8

Zobnina, V., Lambreva, M. D., Rea, G., Campi, G., Polticelli, F., & Sensi, M. (2017). The plastoquinol–plastoquinone exchange mechanism in Photosystem II: Insight from molecular dynamics simulations. Photosynthesis Research, 132(2), 131–145.

Broser, M., Glöckner, C., Gabdulkhakov, A., Guskov, A., Buchta, J., Kern, J., Müh, F., Dau, H., Saenger, W. and Zouni, A. (2011). Structural basis of cyanobacterial photosystem II inhibition by the herbicide terbutryn. Journal of Biological Chemistry, 286(18), 15964–15972.

Fuerst, E.P. and Michael, A.N. (1991). Interactions of herbicides with photosynthetic electron transport. Weed Science, 39(3), 458–464.

Macinnis-Ng, C.M.O. and Ralph, P.J. (2003). Short-term response and recovery of Zostera capricorni photosynthesis after herbicide exposure. Aquatic Botany, 76(1), 1–15.

Ohad, N. and Hirschberg, J. (1992). Mutations in the D1 subunit of photosystem II distinguish between quinone and herbicide binding sites. Plant Cell, 4(3), 273–282.

Oettmeier, W. (1999). Herbicide resistance and supersensitivity in photosystem II. Cellular and Molecular Life Sciences, 55(10), 1255–1277.

Sundby, C., Chow, W.S. and Anderson, J.M. (1993). Effects on Photosystem II function, photoinhibition, and plant performance of the spontaneous mutation of serine-264 in the photosystem II reaction center D1 protein in triazine-resistant Brassica napus L. Plant Physiology, 103(1), 105–113.

Tischer, W. and Strotmann, H. (1977). Relationship between inhibitor binding by chloroplasts and inhibition of photosynthetic electron transport. Biochimica et Biophysica Acta (Bioenergetics), 460(1), 113–125.

Vermaas, W.F., Renger, G. and Arntzen, C.J. (1984). Herbicide/quinone binding interactions in photosystem II. Zeitschrift für Naturforschung C, 39(5), 368–373.

Wilkinson, A.D., Collier, C.J., Flores, F. and Negri, A.P. (2015). Acute and additive toxicity of ten photosystem-II herbicides to seagrass. Scientific Reports, 5, 17443.

Zimmermann, K., Heck, M., Frank, J., Kern, J., Vass, I. and Zouni, A. (2006). Herbicide binding and thermal stability of photosystem II isolated from Thermosynechococcus elongatus. Biochimica et Biophysica Acta (Bioenergetics), 1757(2), 106–114.