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PDBsum entry 1fp0
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Transcription
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PDB id
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1fp0
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Contents |
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* Residue conservation analysis
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References listed in PDB file
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Key reference
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Title
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Solution structure of the phd domain from the kap-1 corepressor: structural determinants for phd, Ring and lim zinc-Binding domains.
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Authors
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A.D.Capili,
D.C.Schultz,
F.J.Rauscheriii,
K.L.Borden.
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Ref.
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EMBO J, 2001,
20,
165-177.
[DOI no: ]
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PubMed id
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Abstract
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Plant homeodomain (PHD) domains are found in >400 eukaryotic proteins, many of
which are transcriptional regulators. Naturally occurring point mutations or
deletions of this domain contribute to a variety of human diseases, including
ATRX syndrome, myeloid leukemias and autoimmune dysfunction. Here we report the
first structural characterization of a PHD domain. Our studies reveal that the
PHD domain from KAP-1 corepressor binds zinc in a cross-brace topology between
anti-parallel ss-strands reminiscent of RING (really interesting new gene)
domains. Using a mutational analysis, we define the structural features required
for transcriptional repression by KAP-1 and explain naturally occurring,
disease-causing mutations in PHD domains of other proteins. From a comparison of
this PHD structure with previously reported RING and LIM (Lin11/Isl-1/Mec-3)
structures, we infer sequence determinants that allow discrimination among PHD,
RING and LIM motifs.
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Figure 4.
Figure 4 Comparison of the KAP-1 PHD, PML RING, IEEHV RING and
RAG1 RING. Superposition of KAP-1 PHD (with blue  -strands,
aa 627 -652) and PML RING (magenta -strands,
aa 56 -81) (A) and RAG1 RING (yellow -strands,
aa 292 -317) (B) from the first metal ligand to the sixth metal
ligand. The white spheres represent zinc atoms with the upper
zinc atom being site I. The orientation of KAP-1 PHD is the same
in both panels. (C) Superposition of zinc-binding site I for
KAP-1 (627 -632, 647 -652), PML (56 -71, 76 -81), IEEHV (7 -12,
28 -33) and RAG1 (292 -297, 312 -317). The metal ligands are
colored according to protein: KAP-1 in blue, PML in magenta,
IEEHV in green and RAG1 in yellow. (D) Superposition of the
conserved hydrophobic core residues N-terminal to metal ligand 5
and C-terminal to metal ligand 6 (L76 and L81 in PML, F28 and
I33 in IEEHV, and F312, I317, F647 and H652 in PHD). The
side-chains are colored as in (C). The core residues from PHD
are noted for clarity. The conserved tryptophan within the PHD
family (W664 in KAP-1) is seen here inserting between the other
core residues, repositioning the core.
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Figure 5.
Figure 5 Amino acid sequence alignment of the PHD, RING and LIM
families. Site I metal ligands are colored in magenta and site
II metal ligands in blue. Conserved hydrophobic core residues
are colored in yellow. DDBJ/EMBL/GenBank accession Nos and PDB
codes: KAP-1 (U78773), TIF1  (AAD17258),
Mi2 (Q14839),
ATRX (P46100), DNMt3A (BAA95556), ING1 (AAG02578), YNJ7_YEAST
(P50947), RBB2_HUMAN (P29375), YM42_YEAST (Q03214), YMW5_YEAST
(Q04779), YA27_SCHPO (Q09698), YAC5_SCHPO (Q09819), AIRE_HUMAN
(O43918), CHD4_HUMAN (Q14839), X169_HUMAN (CAA89909), HT31_ARATH
(Q04996), PRH_ARATH (P48785), CHD3_CAEEL (Q22516), CHD3_HUMAN
(Q12873), YJ89_YEAST (P47156), FALZ_HUMAN (Q12830), YANC_SCHPO
(Q10077), YGN1_YEAST (P53127), YAJ8_SCHPO (Q09908), AF17_HUMAN
(Q09908), YGN1_YEAST (P53127), HRX_HUMAN (Q03164), PML (1bor),
IEEHV (1chc), RAG1 (1RMD), BRCA1 (A58881), BARD1 (NP_00456),
c-Cbl (P22681), MDM2 (CAA41684), MDMX (O15151), MAT (S60157), Z
(P18541), Mel-18 (P35227), Crp1LIM1 and LIM2 (1B8T), CRIPrat
(1IML), Lin-11 (CAA38240), ISL-1 (CAA3749), MEC-3 (S28390),
LMX-1 (B46233).
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The above figures are
reprinted
from an Open Access publication published by Macmillan Publishers Ltd:
EMBO J
(2001,
20,
165-177)
copyright 2001.
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