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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

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

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Author(s):
Aquino, Bruno [1] ; da Silva, Viviane C. H. [1, 2] ; Massirer, Katlin B. [1, 3] ; Arruda, Paulo [1, 2, 3, 4]
Total Authors: 4
Affiliation:
[1] Univ Estadual Campinas UNICAMP, Struct Genom Consortium, BR-13083886 Campinas, SP - Brazil
[2] Joint Res Ctr Genom Appl Climate Change UMIP GenC, BR-13083875 Campinas, SP - Brazil
[3] Univ Estadual Campinas UNICAMP, Ctr Biol Mol Engn Genet, BR-13083875 Campinas, SP - Brazil
[4] Univ Estadual Campinas UNICAMP, Inst Biol, Dept Genet Evolucao, BR-13083970 Campinas, SP - Brazil
Total Affiliations: 4
Document type: Journal article
Source: BMC PLANT BIOLOGY; v. 20, n. 1 APR 15 2020.
Web of Science Citations: 0
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 Leu(240), Tyr(363), and Leu(375) 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. (AU)

FAPESP's process: 14/50897-0 - Open-acess Medicinal Chemistry Centre (OpenMedChem)
Grantee:Paulo Arruda
Support type: Research Projects - Thematic Grants
FAPESP's process: 16/23218-0 - The Genomics for Climate Change Research Center
Grantee:Paulo Arruda
Support type: Research Grants - Research Centers in Engineering Program