Structure of the tandem PX-PH domains of Bem3 from<i>Saccharomyces cerevisiae</i>

Ali, Imtiaz S.; Eu, Sungmin; Koch, Daniel; Bleimling, Nathalie; Goody, Roger S.; Müller, Matthias

doi:10.1107/s2053230x18005915

Cited by 5 publications

(5 citation statements)

References 52 publications

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“…Bem2 and Bem3 are Cdc42 GAP proteins that are found hyperphosphorylated at bud emerging points, which appears to inhibit their GAP activity [ 130 ]. Bem3 contains contiguous PX and PH domains that appear to collaborate in phosphoinositide binding and membrane interactions [ 131 ].…”

Section: Resultsmentioning

confidence: 99%

H2O2 Induces Major Phosphorylation Changes in Critical Regulators of Signal Transduction, Gene Expression, Metabolism and Developmental Networks in Aspergillus nidulans

Carrasco-Navarro

Aguirre

2021

JoF

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Reactive oxygen species (ROS) regulate several aspects of cell physiology in filamentous fungi including the antioxidant response and development. However, little is known about the signaling pathways involved in these processes. Here, we report Aspergillus nidulans global phosphoproteome during mycelial growth and show that under these conditions, H2O2 induces major changes in protein phosphorylation. Among the 1964 phosphoproteins we identified, H2O2 induced the phosphorylation of 131 proteins at one or more sites as well as the dephosphorylation of a larger set of proteins. A detailed analysis of these phosphoproteins shows that H2O2 affected the phosphorylation of critical regulatory nodes of phosphoinositide, MAPK, and TOR signaling as well as the phosphorylation of multiple proteins involved in the regulation of gene expression, primary and secondary metabolism, and development. Our results provide a novel and extensive protein phosphorylation landscape in A. nidulans, indicating that H2O2 induces a shift in general metabolism from anabolic to catabolic, and the activation of multiple stress survival pathways. Our results expand the significance of H2O2 in eukaryotic cell signaling.

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Section: Resultsmentioning

confidence: 99%

H2O2 Induces Major Phosphorylation Changes in Critical Regulators of Signal Transduction, Gene Expression, Metabolism and Developmental Networks in Aspergillus nidulans

Carrasco-Navarro

Aguirre

2021

JoF

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“…Key membrane lipid interactions in PLD1 are denoted. Tandem PX-PH domains modeled from the S. cerevisiae Bem3 structure 50 (PDB entry 6FSF).…”

Section: Figurementioning

confidence: 99%

Crystal structure of human PLD1 provides insight into activation by PI(4,5)P2 and RhoA

et al. 2020

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The signal transduction enzyme phospholipase D1 (PLD1) hydrolyzes phosphatidylcholine to generate the lipid second-messenger phosphatidic acid, which plays roles in disease processes such as thrombosis and cancer. PLD1 is directly and synergistically regulated by Protein Kinase C, Arf and Rho GTPases, and the membrane lipid phosphatidylinositol-4,5-bisphosphate (PIP 2 ). Here, we present a 1.8Å-resolution crystal structure of the human PLD1 catalytic domain that is characterized by a globular fold with a funnel-shaped hydrophobic cavity leading to the active site. Adjacent is a PIP 2 -binding polybasic pocket at the membrane interface that is essential for activity. The C-terminus folds into and contributes part of the catalytic pocket, which harbors a phosphohistidine that mimics an intermediate stage of the catalytic cycle. Mapping of PLD1 mutations that disrupt RhoA activation identifies the RhoA-PLD1 binding interface. This structure sheds light on PLD1 regulation by lipid and protein effectors, enabling rationale inhibitor design for this well-studied therapeutic target.

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“…The PLD2 profile containing the 250 closest homologs was then scanned against the database of the HMM profiles for each of the Protein Data Bank (PDB) crystallographic structures (PDB_mmCIF70 database dated April 10th, 2019). The crystallographic structures of the PX-PH domain tandem of Rem3 from Saccharomyces cerevisiae (PDBid: 6fsf, resolution 2.2 Å [42]) and phosphatidylserine synthase from Haemophilus influenzae Rd KW20 (PDBid: 3hsi, resolution 2.2 Å) were selected as suitable templates for PLD2 segments containing residues 64-314 (PX and PH domains, chain A, template 6fsf) and 331-803 (HKD1 and HKD2 domains, chain B, template 3hsi). Both templates have maximum sequence coverage, highest sequence identity percentage (13% and 15% for 6fsf and 3hsi respectively) and best correspondence between secondary structural elements in their corresponding segments.…”

Section: Homology Modeling Of Pld2mentioning

confidence: 99%

“…The crystallographic structure of PX-PH domain tandem of Rem3 from Saccharomyces cerevisiae (PDBid: 6fsf, resolution 2.2 Å [42]) and that of phosphatidylserine synthase from Haemophilus influenzae Rd KW20 (PDBid: 3hsi, resolution 2.2 Å) were identified as the most suitable templates for PLD2 using HHpred server [39,40] (run dated April-2019). Each of the templates covered different and non-overlapping segments of PLD2.…”

Section: Full-length Model Of Human Pld2mentioning

confidence: 99%

PLD2–PI(4,5)P2 interactions in fluid phase membranes: Structural modeling and molecular dynamics simulations

2020

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Interaction of phospholipase D2 (PLD2) with phosphatidylinositol (4,5)-bisphosphate (PIP 2) is regarded as the critical step of numerous physiological processes. Here we build a fulllength model of human PLD2 (hPLD2) combining template-based and ab initio modeling techniques and use microsecond all-atom molecular dynamics (MD) simulations of the protein in contact with a complex membrane to determine hPLD2-PIP 2 interactions. MD simulations reveal that the intermolecular interactions preferentially occur between specific PIP 2 phosphate groups and hPLD2 residues; the most strongly interacting residues are arginine at the pbox consensus sequence (PX) and pleckstrin homology (PH) domain. Interaction networks indicate formation of clusters at the protein-membrane interface consisting of amino acids, PIP 2 , and 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphatidic acid (POPA); the largest cluster was in the PH domain.

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Structure of the tandem PX-PH domains of Bem3 fromSaccharomyces cerevisiae

Abstract: The structure of the putative membrane-binding tandem PX-PH domain module of the yeast protein Bem3 is reported.

Cited by 5 publications

References 52 publications

H2O2 Induces Major Phosphorylation Changes in Critical Regulators of Signal Transduction, Gene Expression, Metabolism and Developmental Networks in Aspergillus nidulans

H2O2 Induces Major Phosphorylation Changes in Critical Regulators of Signal Transduction, Gene Expression, Metabolism and Developmental Networks in Aspergillus nidulans

Crystal structure of human PLD1 provides insight into activation by PI(4,5)P2 and RhoA

PLD2–PI(4,5)P2 interactions in fluid phase membranes: Structural modeling and molecular dynamics simulations

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