 |
PDBsum entry 2i5o
|
|
|
|
|
 |
Contents |
 |
|
|
|
|
|
|
|
|
|
|
* Residue conservation analysis
|
|
|
|
|
|
|
|
|
|
|
Enzyme class:
|
|
E.C.2.7.7.7
- DNA-directed Dna polymerase.
|
|
|
|
|
|
|
Reaction:
|
|
DNA(n) + a 2'-deoxyribonucleoside 5'-triphosphate = DNA(n+1) + diphosphate
|
|
|
|
|
|
DNA(n)
|
+
|
2'-deoxyribonucleoside 5'-triphosphate
|
=
|
DNA(n+1)
|
+
|
diphosphate
|
|
|
|
|
|
|
|
|
|
|
|
|
Molecule diagrams generated from .mol files obtained from the
KEGG ftp site
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
|
|
|
|
|
|
| |
|
|
| |
|
DOI no:
|
EMBO Rep
8:247-251
(2007)
|
|
PubMed id:
|
|
|
|
|
|
| |
|
Structure of the ubiquitin-binding zinc finger domain of human DNA Y-polymerase eta.
|
|
M.G.Bomar,
M.T.Pai,
S.R.Tzeng,
S.S.Li,
P.Zhou.
|
|
|
|
|
| |
ABSTRACT
|
|
|
|
| |
|
|
The ubiquitin-binding zinc finger (UBZ) domain of human DNA Y-family polymerase
(pol) eta is important in the recruitment of the polymerase to the stalled
replication machinery in translesion synthesis. Here, we report the solution
structure of the pol eta UBZ domain and its interaction with ubiquitin. We show
that the UBZ domain adopts a classical C(2)H(2) zinc-finger structure
characterized by a betabetaalpha fold. Nuclear magnetic resonance titration maps
the binding interfaces between UBZ and ubiquitin to the alpha-helix of the UBZ
domain and the canonical hydrophobic surface of ubiquitin defined by residues
L8, I44 and V70. Although the UBZ domain binds ubiquitin through a single
alpha-helix, in a manner similar to the inverted ubiquitin-interacting motif,
its structure is distinct from previously characterized ubiquitin-binding
domains. The pol eta UBZ domain represents a novel member of the C(2)H(2) zinc
finger family that interacts with ubiquitin to regulate translesion synthesis.
|
|
|
|
|
|
| |
Selected figure(s)
|
|
|
|
| |
|
|
|
|
|
|
Figure 2.
Figure 2 Nuclear magnetic resonance titration shows the binding
interface between the polymerase  UBZ
domain and ubiquitin. (A) Chemical shift perturbations of the
UBZ domain plotted against residue number. Residues with
chemical shift changes greater than 2 
and 1 are
shown in orange (significantly perturbed) and yellow
(perturbed), respectively. (B) A surface representation of the
UBZ domain with significantly perturbed residues (labelled in
black) shown in orange and perturbed residues in yellow. (C)
90° right-handed rotation of (B). (D) Chemical shift
perturbations of residues in ubiquitin calculated and coloured
as in (A). (E) A surface representation of ubiquitin.
Significantly perturbed residues (shown in orange and labelled
in black) and perturbed residues (shown in yellow) are
distributed along the canonical hydrophobic surface defined by
residues V70, I44 (both labelled in red) and L8. (F) 90°
left-handed rotation of (E). Surface representations were
generated by PyMol (DeLano, 2002). pol, polymerase; UBZ,
ubiquitin-binding zinc finger.
|
|
Figure 3.
Figure 3 Proposed model of the polymerase UBZ
domain–ubiquitin complex. (A) A ribbon diagram of the
UIM–ubiquitin complex (PDB entry 1Q0W), with conserved
residues shown in stick model. The orientation of the UIM  -helix
(pink) bound to ubiquitin (green) is indicated by an arrow,
directed from the N to C terminus. (B) A ribbon diagram of the
MIU/IUIM motif (brown) bound to ubiquitin (PDB entry 2FIF), with
the orientation of the -helix
and conserved residues indicated as in (A). (C) Alignment of the
consensus sequences of the UBZ domain with MIU/IUIM and reversed
UIM. The central invariant alanine is highlighted in purple,
conserved hydrophobic residues in yellow, acidic residues in
red, zinc ligands in blue and a highly conserved glutamine
residue in grey. A serine residue at the +4 position in the UIM,
which is replaced by an aspartate in the MIU/IUIM and the UBZ
domains, is shown in blue. (D) A model of the UBZ
domain–ubiquitin complex. The C-terminal cysteine of the UBZ
domain, which was modified by the spin-label reagent MTSL
(denoted as S), and ubiquitin residues, the resonances of which
were severely attenuated during the spin-label titration, are
coloured in blue. (E) Sections of ^1H-^15N HSQC spectra of
ubiquitin, (F) in the presence of the spin-labelled UBZ domain
and (G) after addition of 5 mM dithiothreitol. Note that the
amide resonance of G75[Ub] disappears in the presence of the
spin-labelled UBZ domain (F). IUIM; inverted UIM; MIU, motif
interacting with ubiquitin; PDB, Protein Data Bank; UBZ,
ubiquitin-binding zinc finger; UIM, ubiquitin-interacting motif.
|
|
|
|
|
|
| |
The above figures are
reprinted
by permission from Macmillan Publishers Ltd:
EMBO Rep
(2007,
8,
247-251)
copyright 2007.
|
|
| |
Figures were
selected
by the author.
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
 |
 |
|
Literature references that cite this PDB file's key reference
|
|
|
| |
PubMed id
|
|
Reference
|
|
|
|
|
|
A.Mosbech,
I.Gibbs-Seymour,
K.Kagias,
T.Thorslund,
P.Beli,
L.Povlsen,
S.V.Nielsen,
S.Smedegaard,
G.Sedgwick,
C.Lukas,
R.Hartmann-Petersen,
J.Lukas,
C.Choudhary,
R.Pocock,
S.Bekker-Jensen,
and
N.Mailand
(2012).
DVC1 (C1orf124) is a DNA damage-targeting p97 adaptor that promotes ubiquitin-dependent responses to replication blocks.
|
| |
Nat Struct Mol Biol,
19,
1084-1092.
|
|
|
|
|
|
|
J.E.Sale,
A.R.Lehmann,
and
R.Woodgate
(2012).
Y-family DNA polymerases and their role in tolerance of cellular DNA damage.
|
| |
Nat Rev Mol Cell Biol,
13,
141-152.
|
|
|
|
|
|
|
B.D.Freudenthal,
L.Gakhar,
S.Ramaswamy,
and
M.T.Washington
(2010).
Structure of monoubiquitinated PCNA and implications for translesion synthesis and DNA polymerase exchange.
|
| |
Nat Struct Mol Biol,
17,
479-484.
|
|
|
PDB codes:
|
|
|
|
|
|
|
|
J.D.Pata
(2010).
Structural diversity of the Y-family DNA polymerases.
|
| |
Biochim Biophys Acta,
1804,
1124-1135.
|
|
|
|
|
|
|
M.G.Bomar,
S.D'Souza,
M.Bienko,
I.Dikic,
G.C.Walker,
and
P.Zhou
(2010).
Unconventional ubiquitin recognition by the ubiquitin-binding motif within the Y family DNA polymerases iota and Rev1.
|
| |
Mol Cell,
37,
408-417.
|
|
|
PDB code:
|
|
|
|
|
|
|
|
N.Acharya,
J.H.Yoon,
J.Hurwitz,
L.Prakash,
and
S.Prakash
(2010).
DNA polymerase eta lacking the ubiquitin-binding domain promotes replicative lesion bypass in humans cells.
|
| |
Proc Natl Acad Sci U S A,
107,
10401-10405.
|
|
|
|
|
|
|
V.Schmutz,
R.Janel-Bintz,
J.Wagner,
D.Biard,
N.Shiomi,
R.P.Fuchs,
and
A.M.Cordonnier
(2010).
Role of the ubiquitin-binding domain of Polη in Rad18-independent translesion DNA synthesis in human cell extracts.
|
| |
Nucleic Acids Res,
38,
6456-6465.
|
|
|
|
|
|
|
A.Hishiki,
H.Hashimoto,
T.Hanafusa,
K.Kamei,
E.Ohashi,
T.Shimizu,
H.Ohmori,
and
M.Sato
(2009).
Structural Basis for Novel Interactions between Human Translesion Synthesis Polymerases and Proliferating Cell Nuclear Antigen.
|
| |
J Biol Chem,
284,
10552-10560.
|
|
|
PDB codes:
|
|
|
|
|
|
|
|
E.Laplantine,
E.Fontan,
J.Chiaravalli,
T.Lopez,
G.Lakisic,
M.Véron,
F.Agou,
and
A.Israël
(2009).
NEMO specifically recognizes K63-linked poly-ubiquitin chains through a new bipartite ubiquitin-binding domain.
|
| |
EMBO J,
28,
2885-2895.
|
|
|
|
|
|
|
F.Cordier,
O.Grubisha,
F.Traincard,
M.Véron,
M.Delepierre,
and
F.Agou
(2009).
The Zinc Finger of NEMO Is a Functional Ubiquitin-binding Domain.
|
| |
J Biol Chem,
284,
2902-2907.
|
|
|
|
|
|
|
I.Dikic,
S.Wakatsuki,
and
K.J.Walters
(2009).
Ubiquitin-binding domains - from structures to functions.
|
| |
Nat Rev Mol Cell Biol,
10,
659-671.
|
|
|
|
|
|
|
J.N.Block,
D.J.Zielinski,
V.B.Chen,
I.W.Davis,
E.C.Vinson,
R.Brady,
J.S.Richardson,
and
D.C.Richardson
(2009).
KinImmerse: Macromolecular VR for NMR ensembles.
|
| |
Source Code Biol Med,
4,
3.
|
|
|
|
|
|
|
J.Zeng,
J.Boyles,
C.Tripathy,
L.Wang,
A.Yan,
P.Zhou,
and
B.R.Donald
(2009).
High-resolution protein structure determination starting with a global fold calculated from exact solutions to the RDC equations.
|
| |
J Biomol NMR,
45,
265-281.
|
|
|
PDB code:
|
|
|
|
|
|
|
|
L.Rey,
J.M.Sidorova,
N.Puget,
F.Boudsocq,
D.S.Biard,
R.J.Monnat,
C.Cazaux,
and
J.S.Hoffmann
(2009).
Human DNA polymerase eta is required for common fragile site stability during unperturbed DNA replication.
|
| |
Mol Cell Biol,
29,
3344-3354.
|
|
|
|
|
|
|
P.A.van der Kemp,
M.de Padula,
G.Burguiere-Slezak,
H.D.Ulrich,
and
S.Boiteux
(2009).
PCNA monoubiquitylation and DNA polymerase eta ubiquitin-binding domain are required to prevent 8-oxoguanine-induced mutagenesis in Saccharomyces cerevisiae.
|
| |
Nucleic Acids Res,
37,
2549-2559.
|
|
|
|
|
|
|
H.Inui,
K.S.Oh,
C.Nadem,
T.Ueda,
S.G.Khan,
A.Metin,
E.Gozukara,
S.Emmert,
H.Slor,
D.B.Busch,
C.C.Baker,
J.J.DiGiovanna,
D.Tamura,
C.S.Seitz,
A.Gratchev,
W.H.Wu,
K.Y.Chung,
H.J.Chung,
E.Azizi,
R.Woodgate,
T.D.Schneider,
and
K.H.Kraemer
(2008).
Xeroderma pigmentosum-variant patients from America, Europe, and Asia.
|
| |
J Invest Dermatol,
128,
2055-2068.
|
|
|
|
|
|
|
J.M.Zeng,
C.Tripathy,
P.Zhou,
and
B.R.Donald
(2008).
A HAUSDORFF-BASED NOE ASSIGNMENT ALGORITHM USING PROTEIN BACKBONE DETERMINED FROM RESIDUAL DIPOLAR COUPLINGS AND ROTAMER PATTERNS.
|
| |
Comput Syst Bioinformatics Conf,
2008,
169-181.
|
|
|
|
|
|
|
K.J.Brayer,
and
D.J.Segal
(2008).
Keep your fingers off my DNA: protein-protein interactions mediated by C2H2 zinc finger domains.
|
| |
Cell Biochem Biophys,
50,
111-131.
|
|
|
|
|
|
|
N.Acharya,
J.H.Yoon,
H.Gali,
I.Unk,
L.Haracska,
R.E.Johnson,
J.Hurwitz,
L.Prakash,
and
S.Prakash
(2008).
Roles of PCNA-binding and ubiquitin-binding domains in human DNA polymerase eta in translesion DNA synthesis.
|
| |
Proc Natl Acad Sci U S A,
105,
17724-17729.
|
|
|
|
|
|
|
N.Crosetto,
M.Bienko,
R.G.Hibbert,
T.Perica,
C.Ambrogio,
T.Kensche,
K.Hofmann,
T.K.Sixma,
and
I.Dikic
(2008).
Human Wrnip1 is localized in replication factories in a ubiquitin-binding zinc finger-dependent manner.
|
| |
J Biol Chem,
283,
35173-35185.
|
|
|
|
|
|
|
P.Schreiner,
X.Chen,
K.Husnjak,
L.Randles,
N.Zhang,
S.Elsasser,
D.Finley,
I.Dikic,
K.J.Walters,
and
M.Groll
(2008).
Ubiquitin docking at the proteasome through a novel pleckstrin-homology domain interaction.
|
| |
Nature,
453,
548-552.
|
|
|
PDB codes:
|
|
|
|
|
|
|
|
R.Pabla,
D.Rozario,
and
W.Siede
(2008).
Regulation of Saccharomyces cerevisiae DNA polymerase eta transcript and protein.
|
| |
Radiat Environ Biophys,
47,
157-168.
|
|
|
|
|
|
|
Z.Zhuang,
R.E.Johnson,
L.Haracska,
L.Prakash,
S.Prakash,
and
S.J.Benkovic
(2008).
Regulation of polymerase exchange between Poleta and Poldelta by monoubiquitination of PCNA and the movement of DNA polymerase holoenzyme.
|
| |
Proc Natl Acad Sci U S A,
105,
5361-5366.
|
|
|
|
|
|
|
N.Acharya,
A.Brahma,
L.Haracska,
L.Prakash,
and
S.Prakash
(2007).
Mutations in the ubiquitin binding UBZ motif of DNA polymerase eta do not impair its function in translesion synthesis during replication.
|
| |
Mol Cell Biol,
27,
7266-7272.
|
|
|
|
|
|
|
V.Notenboom,
R.G.Hibbert,
S.E.van Rossum-Fikkert,
J.V.Olsen,
M.Mann,
and
T.K.Sixma
(2007).
Functional characterization of Rad18 domains for Rad6, ubiquitin, DNA binding and PCNA modification.
|
| |
Nucleic Acids Res,
35,
5819-5830.
|
|
|
|
|
|
|
W.Yang,
and
R.Woodgate
(2007).
What a difference a decade makes: insights into translesion DNA synthesis.
|
| |
Proc Natl Acad Sci U S A,
104,
15591-15598.
|
|
|
|
|
|
The most recent references are shown first.
Citation data come partly from CiteXplore and partly
from an automated harvesting procedure. Note that this is likely to be
only a partial list as not all journals are covered by
either method. However, we are continually building up the citation data
so more and more references will be included with time.
Where a reference describes a PDB structure, the PDB
codes are
shown on the right.
|
|
Links
