PDBsum entry: 1fp0

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PDB-id

1fp0

Contents

Description

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Protein chain

Metal ions

_ZN ×2

* Residue conservation analysis

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PDB id:

1fp0

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Transcription

Title:

Solution structure of the phd domain from the kap-1 corepressor

Structure:

Kap-1 corepressor. Chain: a. Fragment: phd domain. Synonym: transcription intermediary factor 1-beta, nuclear corepressor, kap-1, krab-associated protein 1. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562.

UniProt:

Q13263 (TIF1B_HUMAN)

Seq:

Struc:

Seq:

Struc:

Seq:

Struc:

Seq:

835 a.a.

Struc:

88 a.a.*

Key:		PfamA domain			PfamB domain
		Secondary structure			CATH domain

* PDB and UniProt seqs differ at 25 residue positions (black crosses)

Resolution:

not givenÅ

NMR structure:

1 models

Authors:

A.D.Capili,D.C.Schultz,F.J.Rauscher Iii,K.L.B.Borden

Key ref:

A.D.Capili et al. (2001). Solution structure of the PHD domain from the KAP-1 corepressor: structural determinants for PHD, RING and LIM zinc-binding domains.. EMBO J, 20, 165-177. [PubMed id: 11226167] [DOI: 10.1093/emboj/20.1.165]

Date:

29-Aug-00

Release date:

24-Jan-01

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Key reference

DOI no: 10.1093/emboj/20.1.165 EMBO J 20:165-177 (2001)

PubMed id: 11226167

Solution structure of the PHD domain from the KAP-1 corepressor: structural determinants for PHD, RING and LIM zinc-binding domains.

A.D.Capili, D.C.Schultz, F.J.RauscherIII, K.L.Borden.

ABSTRACT

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.

Selected figure(s)

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. 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).

The above figures are reprinted from an Open Access publication published by Macmillan Publishers Ltd: EMBO J (2001, 20, 165-177) copyright 2001.

Figures were selected by an automated process.

Literature references that cite this PDB file's key reference

PubMed id Reference

20012986 M.Mitra, and A.Melis (2010).
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Nat Struct Mol Biol, 15, 626-633.

PDB code: 2ro1

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17947424 S.Ahmed, B.Dul, X.Qiu, and N.C.Walworth (2007).
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Genetics, 177, 1487-1497.

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PDB codes: 2f6j 2f6n 2fsa 2fui 2fuu

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Annu Rev Immunol, 22, 81.

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A new nuclear component of the Wnt signalling pathway.

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J Biol Chem, 277, 6124-6130.

11884585 E.Kalkhoven, H.Teunissen, A.Houweling, C.P.Verrijzer, and A.Zantema (2002).
The PHD type zinc finger is an integral part of the CBP acetyltransferase domain.

Mol Cell Biol, 22, 1961-1970.

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Ubiquitylation of MHC class I by the K3 viral protein signals internalization and TSG101-dependent degradation.

EMBO J, 21, 2418-2429.

11991980 M.E.Lorenzo, J.U.Jung, and H.L.Ploegh (2002).
Kaposi's sarcoma-associated herpesvirus K3 utilizes the ubiquitin-proteasome system in routing class major histocompatibility complexes to late endocytic compartments.

J Virol, 76, 5522-5531.

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Evaluation and classification of RING-finger domains encoded by the Arabidopsis genome.

Genome Biol, 3, RESEARCH0016.

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Targeting histone deacetylase complexes via KRAB-zinc finger proteins: the PHD and bromodomains of KAP-1 form a cooperative unit that recruits a novel isoform of the Mi-2alpha subunit of NuRD.

Genes Dev, 15, 428-443.

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Pf1, a novel PHD zinc finger protein that links the TLE corepressor to the mSin3A-histone deacetylase complex.

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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.