4PKY

ARNT/HIF transcription factor/coactivator complex

PDB DOI: https://doi.org/10.2210/pdb4PKY/pdb

Classification: TRANSCRIPTION/CELL CYCLE
Organism(s): Homo sapiens, Mus musculus
Expression System: Escherichia coli BL21(DE3)
Mutation(s): Yes

Deposited: 2014-05-15 Released: 2015-02-11
Deposition Author(s): Tomchick, D.R., Partch, C.L., Gardner, K.H.

Experimental Data Snapshot

Method: X-RAY DIFFRACTION
Resolution: 3.20 Å
R-Value Free: 0.270
R-Value Work: 0.231
R-Value Observed: 0.233

wwPDB Validation 3D Report Full Report

This is version 1.3 of the entry. See complete history.

Literature

Coiled-coil Coactivators Play a Structural Role Mediating Interactions in Hypoxia-inducible Factor Heterodimerization.

Guo, Y., Scheuermann, T.H., Partch, C.L., Tomchick, D.R., Gardner, K.H.

(2015) J Biol Chem 290: 7707-7721

PubMed: 25627682 Search on PubMedSearch on PubMed Central
DOI: https://doi.org/10.1074/jbc.M114.632786
Primary Citation of Related Structures:
4LPZ, 4PKY

PubMed Abstract:
The hypoxia-inducible factor complex (HIF-α·aryl hydrocarbon receptor nuclear translocator (ARNT)) requires association with several transcription coactivators for a successful cellular response to hypoxic stress. In addition to the conventional global transcription coactivator CREB-binding protein/p300 (CBP/p300) that binds to the HIF-α transactivation domain, a new group of transcription coactivators called the coiled-coil coactivators (CCCs) interact directly with the second PER-ARNT-SIM (PAS) domain of ARNT (ARNT PAS-B). These less studied transcription coactivators play essential roles in the HIF-dependent hypoxia response, and CCC misregulation is associated with several forms of cancer. To better understand CCC protein recruitment by the heterodimeric HIF transcription factor, we used x-ray crystallography, NMR spectroscopy, and biochemical methods to investigate the structure of the ARNT PAS-B domain in complex with the C-terminal fragment of a coiled-coil coactivator protein, transforming acidic coiled-coil coactivator 3 (TACC3). We found that the HIF-2α PAS-B domain also directly interacts with TACC3, motivating an NMR data-derived model suggesting a means by which TACC3 could form a ternary complex with HIF-2α PAS-B and ARNT PAS-B via β-sheet/coiled-coil interactions. These findings suggest that TACC3 could be recruited as a bridge to cooperatively mediate between the HIF-2α PAS-B·ARNT PAS-B complex, thereby participating more directly in HIF-dependent gene transcription than previously anticipated.

Organizational Affiliation

From the Departments of Biophysics and Biochemistry, University of Texas Southwestern Medical Center, Dallas, Texas 75390-8816 and.

Macromolecule Content

Total Structure Weight: 65.48 kDa
Atom Count: 4,092
Modelled Residue Count: 497
Deposited Residue Count: 559
Unique protein chains: 3

Macromolecules

Find similar proteins by:

(by identity cutoff) | 3D Structure

Entity ID: 1
Molecule	Chains	Sequence Length	Organism	Details	Image
Aryl hydrocarbon receptor nuclear translocator	A, D	121	Homo sapiens	Mutation(s): 1 Gene Names: ARNT, BHLHE2
UniProt & NIH Common Fund Data Resources
Find proteins for P27540 (Homo sapiens) Explore P27540 Go to UniProtKB: P27540
PHAROS: P27540 GTEx: ENSG00000143437
Entity Groups
Sequence Clusters	30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt Group	P27540
Sequence Annotations Expand
Reference Sequence

Find similar proteins by:

(by identity cutoff) | 3D Structure

Entity ID: 2
Molecule	Chains	Sequence Length	Organism	Details	Image
Transforming acidic coiled-coil-containing protein 3	B, C, E, F	50	Mus musculus	Mutation(s): 0 Gene Names: Tacc3, Aint
UniProt
Find proteins for Q9JJ11 (Mus musculus) Explore Q9JJ11 Go to UniProtKB: Q9JJ11
Entity Groups
Sequence Clusters	30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt Group	Q9JJ11
Sequence Annotations Expand
Reference Sequence

Find similar proteins by:

(by identity cutoff) | 3D Structure

Entity ID: 3
Molecule	Chains	Sequence Length	Organism	Details	Image
Endothelial PAS domain-containing protein 1	G	117	Homo sapiens	Mutation(s): 1 Gene Names: EPAS1, BHLHE73, HIF2A, MOP2, PASD2
UniProt & NIH Common Fund Data Resources
Find proteins for Q99814 (Homo sapiens) Explore Q99814 Go to UniProtKB: Q99814
PHAROS: Q99814 GTEx: ENSG00000116016
Entity Groups
Sequence Clusters	30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt Group	Q99814
Sequence Annotations Expand
Reference Sequence

Small Molecules

Ligands 1 Unique
ID	Chains	Name / Formula / InChI Key	2D Diagram	3D Interactions
SO4 Query on SO4 Download Ideal Coordinates CCD File SDF format, chain H [auth B] SDF format, chain I [auth B] MOL2 format, chain H [auth B] MOL2 format, chain I [auth B]	H [auth B], I [auth B]	SULFATE ION O₄ S QAOWNCQODCNURD-UHFFFAOYSA-L		Interactions Focus chain H [auth B] Focus chain I [auth B] Interactions & Density Focus chain H [auth B] Focus chain I [auth B]

Experimental Data & Validation

Experimental Data

Method: X-RAY DIFFRACTION
Resolution: 3.20 Å
R-Value Free: 0.270
R-Value Work: 0.231
R-Value Observed: 0.233
Space Group: P 4₁ 2₁ 2

Unit Cell:

Length ( Å )	Angle ( ˚ )
a = 96.136	α = 90
b = 96.136	β = 90
c = 182.841	γ = 90

Software Package:

Software Name	Purpose
HKL-2000	data reduction
PDB_EXTRACT	data extraction
PHASER	phasing
PHENIX	refinement

Structure Validation

View Full Validation Report

Entry History

Deposition Data

Released Date: 2015-02-11

Deposition Author(s):

Tomchick, D.R.

Partch, C.L.

Gardner, K.H.

Revision History (Full details and data files)

Version 1.0: 2015-02-11
Type: Initial release
Version 1.1: 2015-04-01
Changes: Database references
Version 1.2: 2017-11-22
Changes: Database references, Derived calculations, Other, Refinement description, Source and taxonomy
Version 1.3: 2023-09-27
Changes: Data collection, Database references, Refinement description