- 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
-
J. Microbiol. 2023;61(8):755-764. Published online September 8, 2023
-
DOI: https://doi.org/10.1007/s12275-023-00071-3
-
-
896
View
-
8
Download
-
2
Web of Science
-
1
Crossref
-
 Abstract
 PDF
-
Human papillomaviruses (HPVs) can increase the proliferation of infected cells during HPV-driven abnormalities, such as
cervical cancer or benign warts. To date, more than 200 HPV genotypes have been identified, most of which are classified
into three major genera: Alphapapillomavirus, Betapapillomavirus, and Gammapapillomavirus. HPV genomes commonly
encode two structural (L1 and L2) and seven functional (E1, E2, E4–E7, and E8) proteins. L2, the minor structural protein
of HPVs, not only serves as a viral capsid component but also interacts with various human proteins during viral infection. A
recent report revealed that L2 of HPV16 recruits polo-like kinase 1 (Plk1), a master regulator of eukaryotic mitosis and cell
cycle progression, for the delivery of viral DNA to mitotic chromatin during HPV16 infection. In this study, we verified the
direct and potent interactions between the polo-box domain (PBD) of Plk1 and PBD-binding motif (S–S–pT–P)-containing
phosphopeptides derived from L2 of HPV16/HPV18 (high-risk alphapapillomaviruses), HPV5b (low-risk betapapillomavirus),
and HPV4 (low-risk gammapapillomavirus). Subsequent structural determination of the Plk1 PBD bound to the
HPV18 or HPV4 L2-derived phosphopeptide demonstrated that they interact with each other in a canonical manner, in
which electrostatic interactions and hydrogen bonds play key roles in sustaining the complex. Therefore, our structural and
biochemical data imply that Plk1 is a broad binding target of L2 of various HPV genotypes belonging to the Alpha-, Beta-,
and Gammapapillomavirus genera.
-
Citations
Citations to this article as recorded by  - Crystal structures of the μ2 subunit of clathrin-adaptor protein 2 in complex with peptides derived from human papillomavirus 16 E7
Sujin Jung, Dahwan Lim, Joon Sig Choi, Ho-Chul Shin, Seung Jun Kim, Bonsu Ku
Journal of Microbiology.2025; 63(8): e2505003. CrossRef
- 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
-
-
1,043
View
-
4
Download
-
11
Web of Science
-
10
Crossref
-
Abstract
PDF
-
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 - Porcine epidemic diarrhea virus influences the expression of tight junction proteins through the polarity protein PAR6
Tingyu Hu, Ruolan Zhang, Qian Weng, Simin Wang, Yuheng Li, Zhihua Pei, Kai Wang, Guixue Hu
Virus Genes.2026; 62(5): 639. CrossRef - De-regulation of aurora kinases by oncogenic HPV; implications in cancer development and treatment
Kemi Hannah Oladipo, Joanna L. Parish
Tumour Virus Research.2025; 19: 200314. CrossRef - Crystal structures of the μ2 subunit of clathrin-adaptor protein 2 in complex with peptides derived from human papillomavirus 16 E7
Sujin Jung, Dahwan Lim, Joon Sig Choi, Ho-Chul Shin, Seung Jun Kim, Bonsu Ku
Journal of Microbiology.2025; 63(8): e2505003. CrossRef - 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
|
MSK
