title: Structural characterization of an intrinsically unfolded mini-HBX protein from hepatitis B virus.
abstract: The hepatitis B virus x protein (HBX) is expressed in HBV-infected liver cells and can interact with a wide range of cellular proteins. In order to understand such promiscuous behavior of HBX we expressed a truncated mini-HBX protein (named Tr-HBX) (residues 18-142) with 5 Cys → Ser mutations and characterized its structural features using circular dichroism (CD) spectropolarimetry, NMR spectroscopy as well as bioinformatics tools for predicting disorder in intrinsically unstructured proteins (IUPs). The secondary structural content of Tr-HBX from CD data suggests that Tr-HBX is only partially folded. The protein disorder prediction by IUPred reveals that the unstructured region encompasses its N-terminal ~30 residues of Tr-HBX. A two-dimensional (1)H-(15)N HSQC NMR spectrum exhibits fewer number of resonances than expected, suggesting that Tr-HBX is a hybrid type IUP where its folded C-terminal half coexists with a disordered N-terminal region. Many IUPs are known to be capable of having promiscuous interactions with a multitude of target proteins. Therefore the intrinsically disordered nature of Tr-HBX revealed in this study provides a partial structural basis for the promiscuous structure-function behavior of HBX.
authors: Biomedical Translational Research Center, Division of Convergent Biomedical Research, Korea Research Institute of Bioscience and Biotechnology, Daejeon 305-806, Korea.
authors: Si-Hyung
authors: SH
authors: Lee
authors: Eun-Ji
authors: EJ
authors: Cha
authors: Ji-Eun
authors: JE
authors: Lim
authors: Soon-Hwan
authors: SH
authors: Kwon
authors: Do-Hyoung
authors: DH
authors: Kim
authors: Hyeseong
authors: H
authors: Cho
authors: Kyou-Hoon
authors: KH
authors: Han
mesh_terms: D000595:Amino Acid Sequence; D002942:Circular Dichroism / Q000379:methods; D006515:Hepatitis B virus / Q000235:genetics / Q000378:metabolism*; D016297:Mutagenesis, Site-Directed; D019906:Nuclear Magnetic Resonance, Biomolecular; D017433:Protein Structure, Secondary; D058767:Protein Unfolding; D015534:Trans-Activators / Q000737:chemistry* / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D054334:Viral Regulatory and Accessory Proteins
chemical_list: D015534:Trans-Activators; D054334:Viral Regulatory and Accessory Proteins; C057628:hepatitis B virus X protein