KMID : 0624620160490080431
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BMB Reports 2016 Volume.49 No. 8 p.431 ~ p.436
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Structural investigation on the intrinsically disordered N-terminal region of HPV16 E7 protein
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Lee Che-Wook
Kim Do-Hyoung Lee Si-Hyung Su Jiulong Han Kyou-Hoon
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Abstract
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Human papillomavirus (HPV) is the major cause of cervical cancer, a deadly threat to millions of females. The early oncogene product (E7) of the high-risk HPV16 is the primary agent associated with HPV-related cervical cancers. In order to understand how E7 contributes to the transforming activity, we investigated the structural features of the flexible N-terminal region (46 residues) of E7 by carrying out N-15 heteronuclear NMR experiments and replica exchange molecular dynamics simulations. Several NMR parameters as well as simulation ensemble structures indicate that this intrinsically disordered region of E7 contains two transient (10-20% populated) helical pre-structured motifs that overlap with important target binding moieties such as an E2F-mimic motif and a pRb-binding LXCXE segment. Presence of such target-binding motifs in HPV16 E7 provides a reasonable explanation for its promiscuous target-binding behavior associated with its transforming activity.
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KEYWORD
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E7 oncoprotein, Human papillomavirus (HPV), Intrinsically disordered protein (IDP), Molecular dynamics (MD) simulation, Nuclear magnetic resonance (NMR), Pre-structured motif (PreSMo)
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