MSK
Search
- Page Path
- HOME > Search
Journal Article
- Structural and biochemical analysis of the PTPN4 PDZ domain bound to the C-terminal tail of the human papillomavirus E6 oncoprotein
- Hye Seon Lee , Hye-Yeoung Yun , Eun-Woo Lee , Ho-Chul Shin , Seung Jun Kim , Bonsu Ku
- J. Microbiol. 2022;60(4):395-401. Published online January 28, 2022
- DOI: https://doi.org/10.1007/s12275-022-1606-1
- 60 View
- 0 Download
- 8 Web of Science
- 7 Crossref
-
Abstract
- High-risk genotypes of human papillomaviruses (HPVs) are directly implicated in various abnormalities associated with cellular hyperproliferation, including cervical cancer. E6 is one of two oncoproteins encoded in the HPV genome, which recruits diverse PSD-95/Dlg/ZO-1 (PDZ) domain-containing human proteins through its C-terminal PDZ-binding motif (PBM) to be degraded by means of the proteasome pathway. Among the three PDZ domain-containing protein tyrosine phosphatases, protein tyrosine phosphatase non-receptor type 3 (PTPN3) and PTPN13 were identified to be recognized by HPV E6 in a PBM-dependent manner. However, whether HPV E6 associates with PTPN4, which also has a PDZ domain and functions as an apoptosis regulator, remains undetermined. Herein, we present structural and biochemical evidence demonstrating the direct interaction between the PBM of HPV16 E6 and the PDZ domain of human PTPN4 for the first time. X-ray crystallographic structure determination and binding measurements using isothermal titration calorimetry demonstrated that hydrophobic interactions in which Leu158 of HPV16 E6 plays a key role and a network of intermolecular hydrogen bonds sustain the complex formation between PTPN4 PDZ and the PBM of HPV16 E6. In addition, it was verified that the corresponding motifs from several other highrisk HPV genotypes, including HPV18, HPV31, HPV33, and HPV45, bind to PTPN4 PDZ with comparable affinities, suggesting that PTPN4 is a common target of various pathogenic HPV genotypes.
-
Citations
Citations to this article as recorded by
- Bioinformatics Analysis of Human Papillomavirus 16 Integration in Cervical Cancer: Changes in MAGI-1 Expression in Premalignant Lesions and Invasive Carcinoma
Oscar Catalán-Castorena, Olga Lilia Garibay-Cerdenares, Berenice Illades-Aguiar, Rocio Castillo-Sánchez, Ma. Isabel Zubillaga-Guerrero, Marco Antonio Leyva-Vazquez, Sergio Encarnacion-Guevara, Eugenia Flores-Alfaro, Mónica Ramirez-Ruano, Luz del Carmen Al
Cancers.2024; 16(12): 2225. CrossRef - Comparative structural studies on Bovine papillomavirus E6 oncoproteins: Novel insights into viral infection and cell transformation from homology modeling and molecular dynamics simulations
Lucas Alexandre Barbosa de Oliveira Santos, Tales de Albuquerque Leite Feitosa, Marcus Vinicius de Aragão Batista
Genetics and Molecular Biology.2024;[Epub] CrossRef - Crystal Structures of Plk1 Polo-Box Domain Bound to the Human Papillomavirus Minor Capsid Protein L2-Derived Peptide
Sujin Jung, Hye Seon Lee, Ho-Chul Shin, Joon Sig Choi, Seung Jun Kim, Bonsu Ku
Journal of Microbiology.2023; 61(8): 755. CrossRef - The effects of HPV oncoproteins on host communication networks: Therapeutic connotations
Josipa Skelin, Ho Yin Luk, Dražan Butorac, Siaw Shi Boon, Vjekoslav Tomaić
Journal of Medical Virology.2023;[Epub] CrossRef - Structural analysis of human papillomavirus E6 interactions with Scribble PDZ domains
Bryce Z. Stewart, Sofia Caria, Patrick O. Humbert, Marc Kvansakul
The FEBS Journal.2023; 290(11): 2868. CrossRef - Viral manipulation of cell polarity signalling
Airah Javorsky, Patrick O. Humbert, Marc Kvansakul
Biochimica et Biophysica Acta (BBA) - Molecular Cell Research.2023; 1870(7): 119536. CrossRef - Mechanistic role of HPV-associated early proteins in cervical cancer: Molecular pathways and targeted therapeutic strategies
Rahul Bhattacharjee, Sabya Sachi Das, Smruti Sudha Biswal, Arijit Nath, Debangshi Das, Asmita Basu, Sumira Malik, Lamha Kumar, Sulagna Kar, Sandeep Kumar Singh, Vijay Jagdish Upadhye, Danish Iqbal, Suliman Almojam, Shubhadeep Roychoudhury, Shreesh Ojha, J
Critical Reviews in Oncology/Hematology.2022; 174: 103675. CrossRef
- Bioinformatics Analysis of Human Papillomavirus 16 Integration in Cervical Cancer: Changes in MAGI-1 Expression in Premalignant Lesions and Invasive Carcinoma
First
Prev
TOP
