View source for 2i04

[[Image:2i04.jpg|left|200px]]<br /><applet load="2i04" size="450" color="white" frame="true" align="right" spinBox="true" 
caption="2i04, resolution 2.15&Aring;" />
'''X-ray crystal structure of MAGI-1 PDZ1 bound to the C-terminal peptide of HPV18 E6'''<br />

==Overview==
Human papillomavirus (HPV) E6 oncoprotein targets certain tumor, suppressors such as MAGI-1 and SAP97/hDlg for degradation. A short peptide, at the C-terminus of E6 interacts specifically with the PDZ domains of, these tumor suppressors, which is a property unique to high-risk HPVs that, are associated with cervical cancer. The detailed recognition mechanisms, between HPV-E6 and PDZ proteins are unclear. To understand the specific, binding of cellular PDZ substrates by HPV-E6, we have solved the crystal, structures of the complexes containing a peptide from HPV18 E6 bound to, three PDZ domains from MAGI-1 and SAP97/Dlg. The complex crystal, structures reveal novel features of PDZ-peptide recognition that explain, why high-risk HPV-E6 can specifically target these cellular tumor, suppressors for destruction. Moreover, a new peptide-binding loop on these, PDZs is identified as interacting with the E6 peptide. Furthermore, we, have identified an arginine residue, unique to high-risk HPV E6 but, outside the canonical core PDZ recognition motif, that plays an important, role in the binding of the PDZs of both MAGI-I and SAP97/Dlg, mutation of, which abolishes E6's ability to degrade the two proteins. Finally, we have, identified a dimer form of the MAGI-1 PDZ1 in the co-crystal structure, with E6 peptide, which may have functional relevance for MAGI-1 activity., In addition to its novel insights into the biochemistry of PDZ, interactions, this study is important for understanding HPV induced, oncogenesis; this could provide a basis for developing anti-viral and, anti-cancer compounds.

==About this Structure==
2I04 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus] with SO4 as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=2I04 OCA]. 

==Reference==
Structures Of A HPV-E6 Polypeptide Bound To MAGUK Proteins: Mechanisms Of Targeting Tumor Suppressors By A High-Risk HPV Oncoprotein., Zhang Y, Dasgupta J, Ma RZ, Banks L, Thomas M, Chen XS, J Virol. 2007 Jan 31;. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=17267502 17267502]
[[Category: Mus musculus]]
[[Category: Single protein]]
[[Category: Banks, L.]]
[[Category: Chen, X.S.]]
[[Category: Dasgupta, J.]]
[[Category: Thomas, M.]]
[[Category: Zhang, Y.]]
[[Category: SO4]]
[[Category: e6 binding]]
[[Category: pdz]]
[[Category: tumor suppressor]]

''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Wed Nov 21 12:04:39 2007''