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PDBsum entry 3bua
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DNA binding protein
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PDB id
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3bua
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Contents |
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202 a.a.
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14 a.a.
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12 a.a.
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16 a.a.
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12 a.a.
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References listed in PDB file
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Key reference
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Title
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A shared docking motif in trf1 and trf2 used for differential recruitment of telomeric proteins.
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Authors
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Y.Chen,
Y.Yang,
M.Van overbeek,
J.R.Donigian,
P.Baciu,
T.De lange,
M.Lei.
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Ref.
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Science, 2008,
319,
1092-1096.
[DOI no: ]
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PubMed id
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Abstract
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Mammalian telomeres are protected by a six-protein complex: shelterin. Shelterin
contains two closely related proteins (TRF1 and TRF2), which recruit various
proteins to telomeres. We dissect the interactions of TRF1 and TRF2 with their
shared binding partner (TIN2) and other shelterin accessory factors. TRF1
recognizes TIN2 using a conserved molecular surface in its TRF homology (TRFH)
domain. However, this same surface does not act as a TIN2 binding site in TRF2,
and TIN2 binding to TRF2 is mediated by a region outside the TRFH domain.
Instead, the TRFH docking site of TRF2 binds a shelterin accessory factor
(Apollo), which does not interact with the TRFH domain of TRF1. Conversely, the
TRFH domain of TRF1, but not of TRF2, interacts with another
shelterin-associated factor: PinX1.
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Figure 3.
Fig. 3. The TRF2-TIN2 interaction. (A) Co-IP of TIN2 with
cotransfected wild-type and mutant TRF2. (B) Far-Western
analysis of the TIN2 binding region of TRF2 (FL, full-length;
TRF2-  B, TRF2- 1–42). (C)
Superposition of the TIN2[TBM] binding sites in the
TRF1[TRFH]-TIN2[TBM] and TRF2[TRFH]-TIN2[TBM] complexes.
TRF1[TRFH] and TRF2[TRFH] are in green and cyan, respectively.
The TIN2[TBM] peptides bound to TRF1[TRFH] and TRF2[TRFH]are
shown in stick model format and in yellow and magenta,
respectively. (D) TIN2-F258 interacts less efficiently with TRF2
than with TRF1. The F258 binding surfaces of TRF1[TRFH] (top
panel) and TRF2[TRFH] (bottom panel) are shown in magenta
(hydrophobic patch) and blue (hydrophilic patch). The rest of
TRF1[TRFH] and TRF2[TRFH] is in green and cyan, respectively.
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Figure 4.
Fig. 4. The TRF2-Apollo interaction. (A) ITC measurement of the
interactions of TRF1[TRFH] (red) and TRF2[TRFH] (blue) with the
Apollo[TBM] peptide. (B) Overall structure of the dimeric
TRF2[TRFH]-Apollo[TBM] complex. (C) Superposition of Apollo[TBM]
(orange) and TIN2[TBM] (yellow) reveals a shared F/Y-X-L-X-P
motif. (D) Superposition of the TRF2[TRFH]-Apollo[TBM] and the
TRF2[TRFH]-TIN2[TBM] complexes in the vicinity of the Apollo
helix. The TRF2[TRFH] molecules are colored in cyan
(Apollo[TBM]-bound) and gray (TIN2[TBM]-bound), respectively.
(E) Apollo[TBM] binding is TRF2[TRFH]-specific. The surface
representations show that there is no room for Apollo L500 and
Y504 to fit into the peptide binding site of TRF1[TRFH]. (F) In
vitro ITC binding data of wild-type and mutant
TRF2[TRFH]-Apollo[TBM] interactions. (G) Co-IP data show that
Apollo double-mutant L504E/P506 and TRF2 single-mutant F120A
disrupt the in vivo TRF2-Apollo interaction. (H) Localization of
retrovirally expressed HA-tagged wild type and L506E/P508A
double mutant of Apollo in BJ-hTERT cells.
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The above figures are
reprinted
by permission from the AAAs:
Science
(2008,
319,
1092-1096)
copyright 2008.
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