Next Article in Journal
Upregulated Ca2+ Release from the Endoplasmic Reticulum Leads to Impaired Presynaptic Function in Familial Alzheimer’s Disease
Previous Article in Journal
Stem Cell Therapy in Neuroimmunological Diseases and Its Potential Neuroimmunological Complications
 
 
Article

Human Enzyme PADI4 Binds to the Nuclear Carrier Importin α3

1
Instituto de Investigación, Desarrollo e Innovación en Biotecnología Sanitaria de Elche, Universidad Miguel Hernández, 03202 Elche, Spain
2
Instituto de Biocomputación y Física de Sistemas Complejos–Unidad mixta GBsC-CSIC-BIFI, Universidad de Zaragoza, 50018 Zaragoza, Spain
3
CNR-NANOTEC, SS Rende (CS), Department of Physics, University of Calabria, 87036 Rende, Italy
4
Instituto de Investigación Sanitaria Aragón (IIS Aragón), 50009 Zaragoza, Spain
5
Centro de Investigación Biomédica en Red en el Área Temática de Enfermedades Hepáticas y Digestivas (CIBERehd), 28029 Madrid, Spain
6
Departamento de Bioquímica y Biología Molecular y Celular, Universidad de Zaragoza, 50009 Zaragoza, Spain
7
Centro de Biotecnología, Universidad Nacional de Loja, Avda. Pío Jaramillo Alvarado s/n, Loja 110111, Ecuador
8
Unidad de Investigación, Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunidad Valenciana (FISABIO), Hospital General Universitario de Elche, Camí de l’Almazara 11, 03203 Elche, Spain
*
Authors to whom correspondence should be addressed.
Academic Editor: Ursula Stochaj
Cells 2022, 11(14), 2166; https://doi.org/10.3390/cells11142166
Received: 23 May 2022 / Revised: 13 June 2022 / Accepted: 8 July 2022 / Published: 11 July 2022
PADI4 is a peptidyl-arginine deiminase (PADI) involved in the conversion of arginine to citrulline. PADI4 is present in macrophages, monocytes, granulocytes, and several cancer cells. It is the only PADI family member observed within both the nucleus and the cytoplasm. PADI4 has a predicted nuclear localization sequence (NLS) comprising residues Pro56 to Ser83, to allow for nuclear translocation. Recent predictors also suggest that the region Arg495 to Ile526 is a possible NLS. To understand how PADI4 is involved in cancer, we studied the ability of intact PADI4 to bind importin α3 (Impα3), a nuclear transport factor that plays tumor-promoting roles in several cancers, and its truncated species (ΔImpα3) without the importin-binding domain (IBB), by using fluorescence, circular dichroism (CD), and isothermal titration calorimetry (ITC). Furthermore, the binding of two peptides, encompassing the first and the second NLS regions, was also studied using the same methods and molecular docking simulations. PADI4 interacted with both importin species, with affinity constants of ~1–5 µM. The isolated peptides also interacted with both importins. The molecular simulations predict that the anchoring of both peptides takes place in the major binding site of Impα3 for the NLS of cargo proteins. These findings suggest that both NLS regions were essentially responsible for the binding of PADI4 to the two importin species. Our data are discussed within the framework of a cell mechanism of nuclear transport that is crucial in cancer. View Full-Text
Keywords: PADI4; nuclear localization signal; binding; calorimetry; fluorescence; molecular docking; cancer PADI4; nuclear localization signal; binding; calorimetry; fluorescence; molecular docking; cancer
Show Figures

Figure 1

MDPI and ACS Style

Neira, J.L.; Rizzuti, B.; Abián, O.; Araujo-Abad, S.; Velázquez-Campoy, A.; de Juan Romero, C. Human Enzyme PADI4 Binds to the Nuclear Carrier Importin α3. Cells 2022, 11, 2166. https://doi.org/10.3390/cells11142166

AMA Style

Neira JL, Rizzuti B, Abián O, Araujo-Abad S, Velázquez-Campoy A, de Juan Romero C. Human Enzyme PADI4 Binds to the Nuclear Carrier Importin α3. Cells. 2022; 11(14):2166. https://doi.org/10.3390/cells11142166

Chicago/Turabian Style

Neira, José L., Bruno Rizzuti, Olga Abián, Salomé Araujo-Abad, Adrián Velázquez-Campoy, and Camino de Juan Romero. 2022. "Human Enzyme PADI4 Binds to the Nuclear Carrier Importin α3" Cells 11, no. 14: 2166. https://doi.org/10.3390/cells11142166

Find Other Styles
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop