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

Chen, Jiming

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

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

Language

eng

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.

Graduation Semester

2022-12

Type of Resource

Thesis

Handle URL

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

Copyright and License Information

Copyright 2022 Jiming Chen

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