Molecular perspective of protein-ligand selectivity in host and parasitic plants

Witchweed, or Striga hermonthica, is a parasite that destroys $10 billion worth of crops annually. It detects its hosts by detecting strigolactone hormone exuded into the soil by its hosts and using it as a germination stimulant, after which it attaches itself to the root of the host crop and absorbs its nutrients. Despite high sequence, structure, and binding site conservation across different plant species, one strigolactone receptor found in witchweed, ShHTL7 uniquely exhibits picomolar sensitivity to strigolactones, compared to micromolar levels observed in homologs. Previously, the prevailing hypothesis was that this million-fold sensitivity difference is the result of its larger binding pocket volume compared to other receptors, however, this does not account for the dynamics of each of the mechanistic steps of strigolactone signaling. The early steps of strigolactone signaling are binding of the substrate to the receptor, enzymatic hydrolysis of the substrate by the receptor, a conformational change of the receptor to its active state, and association of the active-conformation receptor to its signaling partner. Using a combination of long-timescale molecular dynamics (~3 ms aggregate), QM/MM, and umbrella sampling simulations, we have elucidated mechanistic details of the strigolactone signaling process at atomic resolution in AtD14, a strigolactone receptor found in the non-parasitic plant Arabidopsis thaliana, and ShHTL7. These mechanistic details indicate that while ShHTL7 is more binding with the strigolactone substrate than AtD14, signaling steps that occur after substrate hydrolysis are also key drivers of the selectivity in strigolactone signaling between parasite and host. These mechanistic insights have the potential to aid the design of selective control agents to control witchweed with minimal effect on surrounding host crops.

Name thesis:degree_name

Ph.D.

Level thesis:degree_level

Dissertation

Discipline thesis:degree_discipline

Chemical Engineering

Grantor

University of Illinois at Urbana-Champaign

Year dc:date

2022

Author dc:creator

• Chen, Jiming

Contributors dc:contributor

• Shukla, Diwakar
• Chen, Liqing
• Harley, Brendan A
• Kraft, Mary L

• Protein-ligand Selectivity
• Molecular Dynamics
• Plant Hormone Signaling

Statement dc:rights

• Copyright 2022 Jiming Chen

Language dc:language

en, eng

Handle dc:identifier

https://hdl.handle.net/2142/117631

OAI record oai:identifier

https://www.ideals.illinois.edu/oai-pmh?verb=GetRecord&metadataPrefix=etdms&identifier=oai%3Awww.ideals.illinois.edu%3A2142%2F117631