Molecular perspective of protein-ligand selectivity in host and parasitic plants
Chen, Jiming
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Permalink
https://hdl.handle.net/2142/117631
Description
Title
Molecular perspective of protein-ligand selectivity in host and parasitic plants
Author(s)
Chen, Jiming
Issue Date
2022-10-04
Director of Research (if dissertation) or Advisor (if thesis)
Shukla, Diwakar
Doctoral Committee Chair(s)
Shukla, Diwakar
Committee Member(s)
Chen, Liqing
Harley, Brendan A
Kraft, Mary L
Department of Study
Chemical & Biomolecular Engr
Discipline
Chemical Engineering
Degree Granting Institution
University of Illinois at Urbana-Champaign
Degree Name
Ph.D.
Degree Level
Dissertation
Keyword(s)
Protein-ligand selectivity
Molecular dynamics
Plant hormone signaling
Abstract
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.
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