BMB Rep. 2016; 49(8): 431-436  
Structural investigation on the intrinsically disordered N-terminal region of HPV16 E7 protein
Chewook Lee1,#, Do-Hyoung Kim1,#, Si-Hyung Lee1, Jiulong Su1,2 & Kyou-Hoon Han1,2,*
1Genome Editing Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 34141, 2Department of Bioinformatics, University of Science and Technology, Daejeon 34113, Korea
Correspondence to: Tel: +82-42-860-4250; Fax: +82-42-860-4259; E-mail: khhan600@kribb.re.kr
Published online: August 31, 2016.
© Korean Society for Biochemistry and Molecular Biology. All rights reserved.

Abstract
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.
Keywords: 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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