2b9d: Difference between revisions
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'''Crystal Structure of HPV E7 CR3 domain''' | '''Crystal Structure of HPV E7 CR3 domain''' | ||
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[[Category: Marmorstein, R.]] | [[Category: Marmorstein, R.]] | ||
[[Category: Zhao, K.]] | [[Category: Zhao, K.]] | ||
[[Category: | [[Category: Homodimer]] | ||
[[Category: | [[Category: Zinc finger]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 20:00:49 2008'' | |||
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Revision as of 20:00, 3 May 2008
Crystal Structure of HPV E7 CR3 domain
OverviewOverview
The E7 oncoprotein from human Papillomavirus (HPV) mediates cell transformation in part by binding to the human pRb tumor suppressor protein and E2F transcription factors, resulting in the dissociation of pRb from E2F transcription factors and the premature cell progression into the S-phase of the cell cycle. This activity is mediated by the LXCXE motif and the CR3 zinc binding domain of the E7 protein. In this study we report the x-ray crystal structure of the CR3 region of HPV E7 and a structure-based mutational analysis to investigate its mode of pRb and E2F binding and E2F displacement from pRb. The structure reveals a novel zinc-bound E7-CR3 obligate homodimer that contains two surface patches of sequence conservation. Mutation of residues within these patches reveals that one patch is required for pRb binding, whereas the other is required for E2F binding. We also show that both E7-mediated interactions are required to disrupt pRb.E2F complexes. Based on these studies we present a mechanistic model for how E7 displaces E2F from pRb. Because the CR3 region of HPV E7 has no detectable homology to other human proteins, the structure-function studies presented here provide an avenue for developing small molecule compounds that inhibit HPV-E7-mediated cell transformation.
About this StructureAbout this Structure
2B9D is a Single protein structure of sequence from Human papillomavirus type 1a. Full crystallographic information is available from OCA.
ReferenceReference
Structure of the human Papillomavirus E7 oncoprotein and its mechanism for inactivation of the retinoblastoma tumor suppressor., Liu X, Clements A, Zhao K, Marmorstein R, J Biol Chem. 2006 Jan 6;281(1):578-86. Epub 2005 Oct 24. PMID:16249186 Page seeded by OCA on Sat May 3 20:00:49 2008