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PDBsum entry 1qze
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* Residue conservation analysis
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DOI no:
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Proc Natl Acad Sci U S A
100:12694-12699
(2003)
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PubMed id:
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DNA-repair protein hHR23a alters its protein structure upon binding proteasomal subunit S5a.
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K.J.Walters,
P.J.Lech,
A.M.Goh,
Q.Wang,
P.M.Howley.
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ABSTRACT
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The Rad23 family of proteins, including the human homologs hHR23a and hHR23b,
stimulates nucleotide excision repair and has been shown to provide a novel link
between proteasome-mediated protein degradation and DNA repair. In this work, we
illustrate how the proteasomal subunit S5a regulates hHR23a protein structure.
By using NMR spectroscopy, we have elucidated the structure and dynamic
properties of the 40-kDa hHR23a protein and show it to contain four structured
domains connected by flexible linker regions. In addition, we reveal that these
domains interact in an intramolecular fashion, and by using residual dipolar
coupling data in combination with chemical shift perturbation analysis, we
present the hHR23a structure. By itself, hHR23a adopts a closed conformation
defined by the interaction of an N-terminal ubiquitin-like domain with two
ubiquitin-associated domains. Interestingly, binding of the proteasomal subunit
S5a disrupts the hHR23a interdomain interactions and thereby causes it to adopt
an opened conformation.
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Selected figure(s)
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Figure 3.
Fig. 3. The S5a contact surface on the UBL domain overlaps
significantly with that used to bind the UBA domains. (A)
Residues whose amide protons showed NOE interaction with S5a
(196-307) are colored blue. (B) Those that shift upon addition
of either UBA domain are colored dark blue, and those that only
shift upon addition of the UBA2 domain are light blue. (Left)
The orientation is identical to that of Fig. 1B (Left), and
these are rotated 180° (Right). The program GRASP (51) was
used.
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Figure 4.
Fig. 4. Model of S5a-induced conformational change in
hHR23a. In the absence of S5a, hHR23a undergoes conformational
exchange between two states as each of the UBA domains competes
for the same binding surface on the UBL domain. Addition of S5a
causes hHR23a to adopt an opened conformation as S5a blocks the
UBA-binding surface of the UBL domain.
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Figures were
selected
by an automated process.
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Literature references that cite this PDB file's key reference
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PubMed id
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Reference
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S.Fishbain,
S.Prakash,
A.Herrig,
S.Elsasser,
and
A.Matouschek
(2011).
Rad23 escapes degradation because it lacks a proteasome initiation region.
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Nat Commun,
2,
192.
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Y.W.Chen,
T.Tajima,
and
S.Agrawal
(2011).
The crystal structure of the ubiquitin-like (UbL) domain of human homologue A of Rad23 (hHR23A) protein.
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Protein Eng Des Sel,
24,
131-138.
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PDB code:
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C.Riedinger,
J.Boehringer,
J.F.Trempe,
E.D.Lowe,
N.R.Brown,
K.Gehring,
M.E.Noble,
C.Gordon,
and
J.A.Endicott
(2010).
Structure of Rpn10 and its interactions with polyubiquitin chains and the proteasome subunit Rpn12.
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J Biol Chem,
285,
33992-34003.
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PDB code:
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G.Volkmann,
and
H.Iwaï
(2010).
Protein trans-splicing and its use in structural biology: opportunities and limitations.
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Mol Biosyst,
6,
2110-2121.
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H.Fu,
Y.L.Lin,
and
A.S.Fatimababy
(2010).
Proteasomal recognition of ubiquitylated substrates.
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Trends Plant Sci,
15,
375-386.
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J.M.Winget,
and
T.Mayor
(2010).
The diversity of ubiquitin recognition: hot spots and varied specificity.
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Mol Cell,
38,
627-635.
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L.Skrisovska,
M.Schubert,
and
F.H.Allain
(2010).
Recent advances in segmental isotope labeling of proteins: NMR applications to large proteins and glycoproteins.
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J Biomol NMR,
46,
51-65.
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Y.Li,
J.Yan,
I.Kim,
C.Liu,
K.Huo,
and
H.Rao
(2010).
Rad4 regulates protein turnover at a postubiquitylation step.
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Mol Biol Cell,
21,
177-185.
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J.M.Baugh,
E.G.Viktorova,
and
E.V.Pilipenko
(2009).
Proteasomes can degrade a significant proportion of cellular proteins independent of ubiquitination.
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J Mol Biol,
386,
814-827.
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N.Zhang,
and
K.J.Walters
(2009).
Insights into how protein dynamics affects arylamine N-acetyltransferase catalysis.
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Biochem Biophys Res Commun,
385,
395-401.
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S.Wang,
F.Xin,
X.Liu,
Y.Wang,
Z.An,
Q.Qi,
and
P.G.Wang
(2009).
N-terminal deletion of Peptide:N-glycanase results in enhanced deglycosylation activity.
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PLoS One,
4,
e8335.
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T.Jadhav,
and
M.W.Wooten
(2009).
Defining an Embedded Code for Protein Ubiquitination.
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J Proteomics Bioinform,
2,
316.
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A.M.Goh,
K.J.Walters,
S.Elsasser,
R.Verma,
R.J.Deshaies,
D.Finley,
and
P.M.Howley
(2008).
Components of the ubiquitin-proteasome pathway compete for surfaces on Rad23 family proteins.
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BMC Biochem,
9,
4.
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F.Alber,
F.Förster,
D.Korkin,
M.Topf,
and
A.Sali
(2008).
Integrating diverse data for structure determination of macromolecular assemblies.
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Annu Rev Biochem,
77,
443-477.
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Y.Matiuhin,
D.S.Kirkpatrick,
I.Ziv,
W.Kim,
A.Dakshinamurthy,
O.Kleifeld,
S.P.Gygi,
N.Reis,
and
M.H.Glickman
(2008).
Extraproteasomal Rpn10 restricts access of the polyubiquitin-binding protein Dsk2 to proteasome.
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Mol Cell,
32,
415-425.
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E.Tomlinson,
N.Palaniyappan,
D.Tooth,
and
R.Layfield
(2007).
Methods for the purification of ubiquitinated proteins.
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Proteomics,
7,
1016-1022.
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J.Hamazaki,
K.Sasaki,
H.Kawahara,
S.Hisanaga,
K.Tanaka,
and
S.Murata
(2007).
Rpn10-mediated degradation of ubiquitinated proteins is essential for mouse development.
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Mol Cell Biol,
27,
6629-6638.
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N.Ghaboosi,
and
R.J.Deshaies
(2007).
A conditional yeast E1 mutant blocks the ubiquitin-proteasome pathway and reveals a role for ubiquitin conjugates in targeting Rad23 to the proteasome.
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Mol Biol Cell,
18,
1953-1963.
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Q.Wang,
M.A.Deloia,
Y.Kang,
C.Litchke,
N.Zhang,
M.A.Titus,
and
K.J.Walters
(2007).
The SH3 domain of a M7 interacts with its C-terminal proline-rich region.
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Protein Sci,
16,
189-196.
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PDB code:
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S.Raasi,
and
D.H.Wolf
(2007).
Ubiquitin receptors and ERAD: a network of pathways to the proteasome.
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Semin Cell Dev Biol,
18,
780-791.
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X.Zhu,
R.Ménard,
and
T.Sulea
(2007).
High incidence of ubiquitin-like domains in human ubiquitin-specific proteases.
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Proteins,
69,
1-7.
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Y.Kang,
N.Zhang,
D.M.Koepp,
and
K.J.Walters
(2007).
Ubiquitin receptor proteins hHR23a and hPLIC2 interact.
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J Mol Biol,
365,
1093-1101.
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E.D.Lowe,
N.Hasan,
J.F.Trempe,
L.Fonso,
M.E.Noble,
J.A.Endicott,
L.N.Johnson,
and
N.R.Brown
(2006).
Structures of the Dsk2 UBL and UBA domains and their complex.
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Acta Crystallogr D Biol Crystallogr,
62,
177-188.
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PDB codes:
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I.Kim,
J.Ahn,
C.Liu,
K.Tanabe,
J.Apodaca,
T.Suzuki,
and
H.Rao
(2006).
The Png1-Rad23 complex regulates glycoprotein turnover.
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J Cell Biol,
172,
211-219.
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J.R.Cavey,
S.H.Ralston,
P.W.Sheppard,
B.Ciani,
T.R.Gallagher,
J.E.Long,
M.S.Searle,
and
R.Layfield
(2006).
Loss of ubiquitin binding is a unifying mechanism by which mutations of SQSTM1 cause Paget's disease of bone.
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Calcif Tissue Int,
78,
271-277.
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L.A.Díaz-Martínez,
Y.Kang,
K.J.Walters,
and
D.J.Clarke
(2006).
Yeast UBL-UBA proteins have partially redundant functions in cell cycle control.
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Cell Div,
1,
28.
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Q.Ding,
E.Dimayuga,
and
J.N.Keller
(2006).
Proteasome regulation of oxidative stress in aging and age-related diseases of the CNS.
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Antioxid Redox Signal,
8,
163-172.
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T.Ishii,
M.Funakoshi,
and
H.Kobayashi
(2006).
Yeast Pth2 is a UBL domain-binding protein that participates in the ubiquitin-proteasome pathway.
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EMBO J,
25,
5492-5503.
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A.D.van Dijk,
R.Boelens,
and
A.M.Bonvin
(2005).
Data-driven docking for the study of biomolecular complexes.
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FEBS J,
272,
293-312.
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A.Ohno,
J.Jee,
K.Fujiwara,
T.Tenno,
N.Goda,
H.Tochio,
H.Kobayashi,
H.Hiroaki,
and
M.Shirakawa
(2005).
Structure of the UBA domain of Dsk2p in complex with ubiquitin molecular determinants for ubiquitin recognition.
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Structure,
13,
521-532.
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PDB code:
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B.Kim,
K.S.Ryu,
H.J.Kim,
S.J.Cho,
and
B.S.Choi
(2005).
Solution structure and backbone dynamics of the XPC-binding domain of the human DNA repair protein hHR23B.
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FEBS J,
272,
2467-2476.
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PDB code:
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J.F.Trempe,
N.R.Brown,
E.D.Lowe,
C.Gordon,
I.D.Campbell,
M.E.Noble,
and
J.A.Endicott
(2005).
Mechanism of Lys48-linked polyubiquitin chain recognition by the Mud1 UBA domain.
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EMBO J,
24,
3178-3189.
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PDB code:
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J.H.Lee,
J.M.Choi,
C.Lee,
K.J.Yi,
and
Y.Cho
(2005).
Structure of a peptide:N-glycanase-Rad23 complex: insight into the deglycosylation for denatured glycoproteins.
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Proc Natl Acad Sci U S A,
102,
9144-9149.
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PDB codes:
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L.Hicke,
H.L.Schubert,
and
C.P.Hill
(2005).
Ubiquitin-binding domains.
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Nat Rev Mol Cell Biol,
6,
610-621.
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S.Elsasser,
and
D.Finley
(2005).
Delivery of ubiquitinated substrates to protein-unfolding machines.
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Nat Cell Biol,
7,
742-749.
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S.Raasi,
R.Varadan,
D.Fushman,
and
C.M.Pickart
(2005).
Diverse polyubiquitin interaction properties of ubiquitin-associated domains.
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Nat Struct Mol Biol,
12,
708-714.
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M.Albrecht,
M.Golatta,
U.Wüllner,
and
T.Lengauer
(2004).
Structural and functional analysis of ataxin-2 and ataxin-3.
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Eur J Biochem,
271,
3155-3170.
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M.Kamionka,
and
J.Feigon
(2004).
Structure of the XPC binding domain of hHR23A reveals hydrophobic patches for protein interaction.
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Protein Sci,
13,
2370-2377.
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PDB code:
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Q.Ding,
E.Dimayuga,
W.R.Markesbery,
and
J.N.Keller
(2004).
Proteasome inhibition increases DNA and RNA oxidation in astrocyte and neuron cultures.
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J Neurochem,
91,
1211-1218.
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Q.Wang,
A.M.Goh,
P.M.Howley,
and
K.J.Walters
(2003).
Ubiquitin recognition by the DNA repair protein hHR23a.
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Biochemistry,
42,
13529-13535.
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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
code is
shown on the right.
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Links
