 |
PDBsum entry 2i0l
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Peptide binding protein
|
PDB id
|
|
|
|
2i0l
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
References listed in PDB file
|
|
|
Key reference
|
|
|
Title
|
|
Structures of a human papillomavirus (hpv) e6 polypeptide bound to maguk proteins: mechanisms of targeting tumor suppressors by a high-Risk hpv oncoprotein.
|
|
|
Authors
|
|
Y.Zhang,
J.Dasgupta,
R.Z.Ma,
L.Banks,
M.Thomas,
X.S.Chen.
|
|
|
Ref.
|
|
J Virol, 2007,
81,
3618-3626.
|
|
|
PubMed id
|
|
|
|
|
|
Abstract
|
|
|
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, the mutation of which abolishes E6's ability to
degrade the two proteins. Finally, we have identified a dimer form of MAGI-1 PDZ
domain 1 in the cocrystal 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 antiviral and
anticancer compounds.
|
|
|
Secondary reference #1
|
|
|
Title
|
|
Hpv e6 and maguk protein interactions: determination of the molecular basis for specific protein recognition and degradation.
|
|
|
Authors
|
|
M.Thomas,
B.Glaunsinger,
D.Pim,
R.Javier,
L.Banks.
|
|
|
Ref.
|
|
Oncogene, 2001,
20,
5431-5439.
|
|
|
PubMed id
|
|
|
|
|
|
|
|
|
|
|
|
|
