Data_Sheet_1_Prolyl Isomerase Pin1 Regulates the Stability of Hepatitis B Virus Core Protein.PDF (4.02 MB)
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Data_Sheet_1_Prolyl Isomerase Pin1 Regulates the Stability of Hepatitis B Virus Core Protein.PDF

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posted on 31.01.2020, 08:10 authored by Mayuko Nishi, Kei Miyakawa, Satoko Matsunaga, Hajera Khatun, Yutaro Yamaoka, Koichi Watashi, Masaya Sugiyama, Hirokazu Kimura, Takaji Wakita, Akihide Ryo

The dynamic interplay between virus and host proteins is critical for establishing efficient viral replication and virus-induced pathogenesis. Phosphorylation-dependent prolyl isomerization by Pin1 provides a unique mechanism of molecular switching to control both protein function and stability. We demonstrate here that Pin1 binds and stabilizes hepatitis B virus core protein (HBc) in a phosphorylation-dependent manner, and promotes the efficient viral propagation. Phos-tag gel electrophoresis with various site-directed mutants of HBc revealed that Thr160 and Ser162 residues within the C terminal arginine-rich domain are phosphorylated concomitantly. GST pull-down assay and co-immunoprecipitation analysis demonstrated that Pin1 associated with phosphorylated HBc at the Thr160-Pro and Ser162-Pro motifs. Chemical or genetic inhibition of Pin1 significantly accelerated the rapid degradation of HBc via a lysosome-dependent pathway. Furthermore, we found that the pyruvate dehydrogenase phosphatase catalytic subunit 2 (PDP2) could dephosphorylate HBc at the Pin1-binding sites, thereby suppressing Pin1-mediated HBc stabilization. Our findings reveal an important regulatory mechanism of HBc stability catalyzed by Pin1 and may facilitate the development of new antiviral therapeutics targeting Pin1 function.

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