8JOY

Plk1 polo-box domain bound to HPV4 L2 residues 251-257 with pThr255

8JOY の概要

• エントリーDOI: 10.2210/pdb8joy/pdb
• 分子名称: Serine/threonine-protein kinase PLK1, Peptide from Minor capsid protein L2 (3 entities in total)
• 機能のキーワード: plk1, polo-box domain, pbd, hpv, l2, hpv4, cell cycle
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 27033.74

構造登録者

Ku, B.,Jung, S. (登録日: 2023-06-09, 公開日: 2023-10-11, 最終更新日: 2024-10-30)

主引用文献

Jung, S.,Lee, H.S.,Shin, H.C.,Choi, J.S.,Kim, S.J.,Ku, B.
Crystal Structures of Plk1 Polo-Box Domain Bound to the Human Papillomavirus Minor Capsid Protein L2-Derived Peptide.
J.Microbiol, 61:755-764, 2023

PubMed Abstract: 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.

PubMed: 37684534
DOI: 10.1007/s12275-023-00071-3

実験手法

X-RAY DIFFRACTION (2.61 Å)