The armadillo-repeat domain of plakophilin 1 binds the C-terminal sterile alpha motif (SAM) of p73.

Biochim Biophys Acta Gen Subj

Instituto de Biocomputación y Física de Sistemas Complejos (BIFI), Joint Units IQFR-CSIC-BIFI, GBsC-CSIC-BIFI, Universidad de Zaragoza, 50009 Zaragoza, Spain; Instituto de Investigación Sanitaria Aragón (IIS Aragón), 50009 Zaragoza, Spain; Fundacion ARAID, Government of Aragon, 50009 Zaragoza, Spain; Centro de Investigación Biomédica en Red en el Área Temática de Enfermedades Hepáticas y Digestivas (CIBERehd), Madrid, Spain; Departamento de Bioquímica y Biología Molecular y Celular, Universidad de Zaragoza, 50009 Zaragoza, Spain.

Published: July 2021

Background: Plakophilin 1 (PKP1) is a component of desmosomes, which are key structural components for cell-cell adhesion, and can also be found in other cell locations. The p53, p63 and p73 proteins belong to the p53 family of transcription factors, playing crucial roles in tumour suppression. The α-splice variant of p73 (p73α) has at its C terminus a sterile alpha motif (SAM); such domain, SAMp73, is involved in the interaction with other macromolecules.

Methods: We studied the binding of SAMp73 with the armadillo domain of PKP1 (ARM-PKP1) in the absence and the presence of 100 mM NaCl, by using several biophysical techniques, namely fluorescence, far-ultraviolet circular dichroism (CD), nuclear magnetic resonance (NMR), isothermal titration calorimetry (ITC), and molecular docking and simulations.

Results: Association was observed between the two proteins, with a dissociation constant of ~5 μM measured by ITC and fluorescence in the absence of NaCl. The binding region of SAMp73 involved residues of the so-called "middle-loop-end-helix" binding region (i.e., comprising the third helix, together with the C terminus of the second one, and the N-cap of the fourth), as shown by N, H- HSQC-NMR spectra. Molecular modelling provided additional information on the possible structure of the binding complex.

Conclusions: This newly-observed interaction could have potential therapeutic relevance in the tumour pathways where PKP1 is involved, and under conditions when there is a possible inactivation of p53.

General Significance: The discovery of the binding between SAMp73 and ARM-PKP1 suggests a functional role for their interaction, including the possibility that SAMp73 could assist PKP1 in signalling pathways.

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bbagen.2021.129914DOI Listing

Publication Analysis

Top Keywords

sterile alpha
8
alpha motif
8
motif sam
8
samp73 involved
8
binding samp73
8
binding region
8
samp73
5
binding
5
armadillo-repeat domain
4
domain plakophilin
4

Similar Publications

Introduction: Platelet transfusion has been therapeutically used in patients with thrombocytopenia and platelet function defects over the years. The use of advanced techniques may add value in assessing the quality of platelet products. The aim of the study was to assess stored platelet concentrates (PCs) prepared in blood banks for platelet indices, clot strength, and platelet function.

View Article and Find Full Text PDF

Diosmetin alleviates TNFα-induced liver inflammation by improving liver sinusoidal endothelial cell dysfunction.

Biomed Pharmacother

January 2025

Jagiellonian University, Faculty of Biochemistry, Biophysics and Biotechnology, Department of General Biochemistry, Gronostajowa 7, Kraków 30-387, Poland. Electronic address:

Sterile inflammation contributes to the development of many liver diseases including non-alcoholic fatty liver disease. Tumor necrosis factor alpha (TNFα) is a key cytokine driving liver inflammation primarily through pro-inflammatory activation of liver sinusoidal endothelial cells (LSEC). The knowledge of whether modulating LSEC activation can alleviate liver inflammation is scarce.

View Article and Find Full Text PDF

Gap junction intercellular communications regulates activation of SARM1 and protects against axonal degeneration.

Cell Death Dis

January 2025

State Key Laboratory of Chemical Oncogenomics, Key Laboratory of Chemical Genomics, Peking University Shenzhen Graduate School, Shenzhen, 518055, China.

Sterile alpha and Toll/interleukin-1 receptor motif containing 1 (SARM1), a nicotinamide adenine dinucleotide (NAD)-utilizing enzyme, mediates axon degeneration (AxD) in various neurodegenerative diseases. It is activated by nicotinamide mononucleotide (NMN) to produce a calcium messenger, cyclic ADP-ribose (cADPR). This activity is blocked by elevated NAD level.

View Article and Find Full Text PDF

As global change threatens avian biodiversity, understanding species responses to environmental perturbations due to radiation emitted by enormous increase in the application of wireless communication is very urgent. The study investigates the effect of MW radiation on redox balance, stress level, male fertility and the efficacy of Withania somnifera (WS) root extract (100 mg/kg body weight) orally administered in 8 weeks old mature male Japanese quail exposed to 2.4 GHz MW radiation for 2 h/day for 30 days with power density = 0.

View Article and Find Full Text PDF

Functional conservation and divergence of arabidopsis VENOSA4 and human SAMHD1 in DNA repair.

Heliyon

January 2025

Instituto de Bioingeniería, Universidad Miguel Hernández, Campus de Elche, 03202, Elche, Spain.

The human deoxyribonucleoside triphosphatase (dNTPase) Sterile alpha motif and histidine-aspartate domain containing protein 1 (SAMHD1) has a dNTPase-independent role in repairing DNA double-strand breaks (DSBs) by homologous recombination (HR). Here, we show that VENOSA4 (VEN4), the probable ortholog of SAMHD1, also functions in DSB repair by HR. The loss-of-function mutants showed increased DNA ploidy and deregulated DNA repair genes, suggesting DNA damage accumulation.

View Article and Find Full Text PDF

Want 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!