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106 a.a.
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88 a.a.
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150 a.a.
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15 a.a.
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* Residue conservation analysis
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PDB id:
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Transcription
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Title:
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Structure of a hif-1a-pvhl-elonginb-elonginc complex
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Structure:
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Elongin b. Chain: b. Engineered: yes. Elongin c. Chain: c. Engineered: yes. Von hippel-lindau disease tumor suppressor. Chain: v. Synonym: vhl.
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Source:
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Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562. Synthetic: yes. Other_details: the peptide was chemically synthesized. The sequence of the protein is naturally found in homo sapiens.
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Biol. unit:
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Tetramer (from
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Resolution:
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1.85Å
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R-factor:
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0.196
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R-free:
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0.236
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Authors:
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J.-H.Min,H.Yang,M.Ivan,F.Gertler,W.G.Kaelin Jr.,N.P.Pavletich
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Key ref:
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J.H.Min
et al.
(2002).
Structure of an HIF-1alpha -pVHL complex: hydroxyproline recognition in signaling.
Science,
296,
1886-1889.
PubMed id:
DOI:
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Date:
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30-Apr-02
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Release date:
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12-Jun-02
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PROCHECK
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Headers
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References
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Q15370
(ELOB_HUMAN) -
Elongin-B from Homo sapiens
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Seq:
Struc:
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118 a.a.
106 a.a.
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Q15369
(ELOC_HUMAN) -
Elongin-C from Homo sapiens
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Seq:
Struc:
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112 a.a.
88 a.a.
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DOI no:
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Science
296:1886-1889
(2002)
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PubMed id:
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Structure of an HIF-1alpha -pVHL complex: hydroxyproline recognition in signaling.
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J.H.Min,
H.Yang,
M.Ivan,
F.Gertler,
W.G.Kaelin,
N.P.Pavletich.
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ABSTRACT
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The ubiquitination of the hypoxia-inducible factor (HIF) by the von
Hippel-Lindau tumor suppressor (pVHL) plays a central role in the cellular
response to changes in oxygen availability. pVHL binds to HIF only when a
conserved proline in HIF is hydroxylated, a modification that is
oxygen-dependent. The 1.85 angstrom structure of a 20-residue HIF-1alpha
peptide-pVHL-ElonginB-ElonginC complex shows that HIF-1alpha binds to pVHL in an
extended beta strand-like conformation. The hydroxyproline inserts into a gap in
the pVHL hydrophobic core, at a site that is a hotspot for tumorigenic
mutations, with its 4-hydroxyl group recognized by buried serine and histidine
residues. Although the beta sheet-like interactions contribute to the stability
of the complex, the hydroxyproline contacts are central to the strict
specificity characteristic of signaling.
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Selected figure(s)
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Figure 1.
Fig. 1. The HIF-1  destruction
sequence binds the  domain of
pVHL in an extended
strand-like conformation. (A) Schematic representation of the
15-residue portion of the HIF-1 destruction
sequence bound to the domain of
pVHL in the pVHL-ElonginB-ElonginC complex. The portion of HIF-1
that
adopts a continuous -strand
conformation is indicated by a wide arrow. HIF-1 is in
blue, Hyp564 in yellow, pVHL in red, ElonginB in magenta, and
ElonginC in green. C, COOH-terminus; N, NH[2]-terminus. The
figures are prepared with MOLSCRIPT (27), GL_RENDER, and POVRAY
(28). (B) Alignment of the first destruction sequence in the
ODDs of HIF-1 orthologs
and HIF-2 and HIF-3
paralogs,
highlighting residues identical in seven of the nine sequences.
The N and the C segments of human HIF-1 are
indicated in red. The putative N and C segments of the second
destruction sequences of HIF-1 and HIF-2
orthologs
are aligned below. The reported second destruction sequence is
38 residues long, and only a 23-residue region that aligns with
the first destruction sequence is shown. Dashes indicate gaps
relative to the seven-residue spacing between the putative N and
C segments of the second destruction sequence.
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Figure 2.
Fig. 2. The contacts made by the N segment, and in particular
by Hyp564, are central to the binding of HIF-1 to pVHL.
(A) Closeup view of the HIF-1 N
segment-pVHL contacts. The side chains of HIF-1 and pVHL
are colored in light blue and yellow, respectively. The
backbones of HIF-1 and pVHL
are in medium blue and red, respectively. The dotted lines
indicate hydrogen bonds between the Gln67 O  [1], Tyr98
O  , His110 NH,
and His110 CO groups of pVHL, and the Leu562 NH, Hyp564 CO,
Tyr565 NH, and Tyr565 CO groups of HIF-1 . In pVHL,
only the structural elements that make up the HIF-1 binding
site are shown for clarity. (B) Surface representation of pVHL
colored according to the degree of conservation in the pVHL
orthologs in Fig. 1B. Yellow indicates identity in five
orthologs (labeled residues), light green in four, and dark
green in three. The HIF-1 side
chains are in light blue, and the backbone is in medium blue.
The N segment is in an orientation similar to that of (A). The
approximate boundaries of the N and C segments and of the bulge
are indicated. (C) Closeup view of the bulge and the C-segment
area of the HIF-1 peptide-pVHL
complex. The 567 P-M-D-D 571 bulge sequence does not contact
pVHL, but forms an intramolecular -turn
hydrogen bond (CO of Pro567 and NH of Asp569). The Asp570 side
chain of HIF-1 is omitted
for clarity.
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The above figures are
reprinted
by permission from the AAAs:
Science
(2002,
296,
1886-1889)
copyright 2002.
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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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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.
|
| |
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