Crystal structure of DRIK1, a stress-responsive receptor-like pseudokinase, reveals the molecular basis for the absence of ATP binding

DOI: 10.1186/s12870-020-2328-3

Authors: Bruno Aquino (Structural Genomics Consortium, Universidade Estadual de Campinas – UNICAMP) , Viviane C. H. Da Silva (Structural Genomics Consortium, Universidade Estadual de Campinas – UNICAMP; Joint Research Center for Genomic Applied to Climate Change (UMIP-GenClima)) , Katlin B. Massirer (Structural Genomics Consortium, Universidade Estadual de Campinas – UNICAMP; Centro de Biologia Molecular e Engenharia Genética, Universidade Estadual de Campinas (UNICAMP)) , Paulo Arruda (Structural Genomics Consortium, Universidade Estadual de Campinas – UNICAMP; Joint Research Center for Genomic Applied to Climate Change (UMIP-GenClima); Universidade Estadual de Campinas (UNICAMP))
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Bmc Plant Biology , VOL 20

State: Published (Approved)
Published: April 2020
Diamond Proposal Number(s): 15433

Abstract: Background :Plants reprogram metabolism and development to rapidly adapt to biotic and abiotic stress. Protein kinases play a significant role in this process by phosphorylating protein substrates that activate or inactivate signaling cascades that regulate cellular and metabolic adaptations. Despite their importance in plant biology, a notably small fraction of the plant kinomes has been studied to date. Results: In this report, we describe ZmDRIK1, a stress-responsive receptor-like pseudokinase whose expression is downregulated under water restriction. We show the structural features and molecular basis of the absence of ATP binding exhibited by ZmDRIK1. The ZmDRIK1 kinase domain lacks conserved amino acids that are essential for phosphorylation activity. The crystal structure of the ZmDRIK1 kinase domain revealed the presence of a spine formed by the side chain of the triad Leu240, Tyr363, and Leu375 that occludes the ATP binding pocket. Although ZmDRIK1 is unable to bind nucleotides, it does bind the small molecule ENMD-2076 which, in a cocrystal structure, revealed the potential to serve as a ZmDRIK1 inhibitor. Conclusion: ZmDRIK1 is a novel receptor-like pseudokinase responsive to biotic and abiotic stress. The absence of ATP binding and consequently, the absence of phosphorylation activity, was proven by the crystal structure of the apo form of the protein kinase domain. The expression profiling of the gene encoding ZmDRIK1 suggests this kinase may play a role in downregulating the expression of stress responsive genes that are not necessary under normal conditions. Under biotic and abiotic stress, ZmDRIK1 is down-regulated to release the expression of these stress-responsive genes.

Subject Areas: Biology and Bio-materials, Environment


Instruments: I03-Macromolecular Crystallography

Other Facilities: 24-ID-E at Advanced Photon Source

Added On: 30/04/2020 10:59

Documents:
s12870-020-2328-3.pdf

Discipline Tags:

Plant science Earth Sciences & Environment Climate Change Genetics Structural biology Life Sciences & Biotech

Technical Tags:

Diffraction Macromolecular Crystallography (MX)