Protein Phosphatase 2A (PP2A) plays an essential role in many aspects of cellular physiology. The PP2A holoenzyme consists of a heterodimeric core enzyme, which comprises a scaffolding subunit and a catalytic subunit, and a variable regulatory subunit. Here we report the crystal structure of the heterotrimeric PP2A holoenzyme involving the regulatory subunit B'/B56/PR61. Surprisingly, the B'/PR61 subunit has a HEAT-like (huntingtin-elongation-A subunit-TOR-like) repeat structure, similar to that of the scaffolding subunit. The regulatory B'/B56/PR61 subunit simultaneously interacts with the catalytic subunit as well as the conserved ridge of the scaffolding subunit. The carboxyterminus of the catalytic subunit recognizes a surface groove at the interface between the B'/B56/PR61 subunit and the scaffolding subunit. Compared to the scaffolding subunit in the PP2A core enzyme, formation of the holoenzyme forces the scaffolding subunit to undergo pronounced conformational rearrangements. This structure reveals significant ramifications for understanding the function and regulation of PP2A.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.cell.2006.11.033 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Functional differentiation of human dental pulp stem cells into neuron-like cells exhibiting electrophysiological activity.
Stem Cell Res Ther
January 2025
Department of Cell Biology and Histology, University of the Basque Country UPV/EHU, Leioa, Bizkaia, 48940, Spain.
Background And Aim: Human dental pulp stem cells (hDPSCs) constitute a promising alternative for central nervous system (CNS) cell therapy. Unlike other human stem cells, hDPSCs can be differentiated, without genetic modification, to neural cells that secrete neuroprotective factors. However, a better understanding of their real capacity to give rise to functional neurons and integrate into synaptic networks is still needed.
View Article and Find Full Text PDFYeast Eukaryotic Initiation Factor 4B Remodels the MRNA Entry Site on the Small Ribosomal Subunit.
Biochemistry
January 2025
Department of Developmental Biology and Genetics, Indian Institute of Science, Bengaluru 560012, India.
Eukaryotic Initiation Factor 4 (eIF4) is a group of factors that activates mRNA for translation and recruit 43S preinitiation complex (PIC) to the mRNA 5' end, forming the 48S PIC. The eIF4 factors include mRNA 5' cap-binding protein eIF4E, ATP-dependent RNA helicase eIF4A, and scaffold protein eIF4G, which anchors eIF4A and eIF4E. Another eIF4 factor, eIF4B, stimulates the RNA helicase activity of eIF4A and facilitates mRNA recruitment.
View Article and Find Full Text PDFDirect observation of small molecule activator binding to single PR65 protein.
NPJ Biosens
January 2025
Department of Electrical Engineering, University of Victoria, Victoria, BC V8W 3P6 Canada.
The reactivation of heterotrimeric protein phosphatase 2A (PP2A) through small molecule activators is of interest to therapeutic intervention due to its dysregulation, which is linked to chronic conditions. This study focuses on the PP2A scaffold subunit PR65 and a small molecule activator, ATUX-8385, designed to bind directly to this subunit. Using a label-free single-molecule approach with nanoaperture optical tweezers (NOT), we quantify its binding, obtaining a dissociation constant of 13.
View Article and Find Full Text PDFKnoevenagel-IMHDA and -IMSDA sequences for the synthesis of chiral condensed O,N-, S,N- and N-heterocycles.
RSC Adv
January 2025
Department of Organic Chemistry, University of Debrecen Egyetem Square 1 Debrecen 4032 Hungary
Domino Knoevenagel-cyclization reactions of styrene substrates, containing an -(-formyl)aryl subunit, were carried out with -substituted 2-cyanoacetamides to prepare tetrahydro-4-pyrano[3,4-]quinolone and hexahydrobenzo[]phenanthridine derivatives by competing IMHDA and IMSDA cyclization, respectively. The diastereoselective IMHDA step with α,β-unsaturated amide, thioamide, ester and ketone subunits as a heterodiene produced condensed chiral tetrahydropyran or thiopyran derivatives, which in the case of Meldrum's acid were reacted further with amine nucleophiles in a multistep domino sequence. In order to simplify the benzene-condensed tricyclic core of the targets and get access to hexahydro-1-pyrano[3,4-]pyridine derivatives, a truncated substrate was reacted with cyclic and acyclic active methylene reagents in diastereoselective Knoevenagel-IMHDA reactions to prepare novel condensed heterocyclic scaffolds.
View Article and Find Full Text PDFA synthetic cyclic peptide for promoting antigen presentation and immune activation.
NPJ Vaccines
January 2025
School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, Australia.
Cyclic peptides are often used as scaffolds for the multivalent presentation of drug molecules due to their structural stability and constrained conformation. We identified a cyclic deca-peptide incorporating lipoamino acids for delivering T helper and B cell epitopes against group A Streptococcus (GAS), eliciting robust humoral immune responses. In this study, we assessed the function-immunogenicity relationship of the multi-component vaccine candidate (referred to as VC-13) to elucidate a mechanism of action.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!