Portal de investigación
The armadillo-repeat domain of Plakophilin 1 binds to human enzyme PADI4
Autores de FISABIO
Autores ajenos a FISABIO
- Neira, JL
- Rizzuti, B
- Araujo-Abad, S
- Abian, O
- Farez-Vidal, ME
- Velazquez-Campoy, A
Grupos de Investigación
Abstract
Plakophilin 1 (PKP1), a member of the armadillo repeat family of proteins, is a key structural component of cellcell adhesion scaffolds, although it can also be found in other cell locations, including the cytoplasm and the nucleus. PADI4 (peptidyl-arginine deiminase 4) is one of the human isoforms of a family of enzymes engaged in the conversion of arginine to citrulline, and is present in monocytes, macrophages, granulocytes, and in several types of cancer cells. It is the only family member observed both within the nucleus and the cytoplasm under ordinary conditions. We studied the binding of the armadillo domain of PKP1 (ARM-PKP1) with PADI4, by using several biophysical methods, namely fluorescence, far-ultraviolet (far-UV) circular dichroism (CD), isothermal titration calorimetry (ITC), and molecular simulations; furthermore, binding was also tested by Western-blot (WB) analyses. Our results show that there was binding between the two proteins, with a dissociation constant in the low micromolar range (similar to 1 mu M). Molecular modelling provided additional information on the possible structure of the binding complex, and especially on the binding hot-spot predicted for PADI4. This is the first time that the interaction between these two proteins has been described and studied. Our findings could be of importance to understand the development of tumors, where PKP1 and PADI4 are involved. Moreover, our findings pave the way to describe the formation of neutrophil extracellular traps (NETs), whose construction is modulated by PADI4, and which mediate the proteolysis of cell-cell junctions where PKP1 intervenes.
Datos de la publicación
- ISSN/ISSNe:
- 1570-9639, 1878-1454
- Tipo:
- Article
- Páginas:
- 140868-140868
- PubMed:
- 36372391
BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS Elsevier BV
Citas Recibidas en Web of Science: 7
Documentos
- No hay documentos
Filiaciones
Keywords
- PADI4; Protein-protein interactions; Isothermal titration calorimetry; Molecular dynamics
Financiación
Ayudas competitivas y Estudios Clínicos asociados
Proyecto Mochila Miguel Servet Camino de Juan
Investigador Principal: MEURI DEL CAMINO DE JUAN ROMERO
CP19/00095 . INSTITUTO CARLOS III . 2020
Identificación de nuevas dianas terapéuticas para el pronóstico y la mejora del tratamiento del glioblastoma
Investigador Principal: MEURI DEL CAMINO DE JUAN ROMERO
PI22/00824 . INSTITUTO CARLOS III . 2023