PDBsum entry 4cy1

Transcription

PDB id: 4cy1

Contents

Protein chains

303 a.a.

14 a.a.

Ligands

GOL ×3

Waters ×321

PDB id:

4cy1

Name:

Transcription

Title:

Crystal structure of the kansl1-wdr5 complex.

Structure:

Wd repeat-containing protein 5. Chain: a, b. Fragment: residues 23-334. Synonym: bmp2-induced 3-kb gene protein. Engineered: yes. Kat8 regulatory nsl complex subunit 1. Chain: c, d. Fragment: residues 585-598. Synonym: kansl1, mll1/mll complex subunit kansl1, msl1 homolog 1,

Source:

Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 469008. Expression_system_variant: star. Synthetic: yes. Organism_taxid: 9606

Resolution:

1.50Å R-factor: 0.171 R-free: 0.183

Authors:

J.Dias,J.Brettschneider,S.Cusack,J.Kadlec

Key ref:

J.Dias et al. (2014). Structural analysis of the KANSL1/WDR5/KANSL2 complex reveals that WDR5 is required for efficient assembly and chromatin targeting of the NSL complex. Genes Dev, 28, 929-942. PubMed id: 24788516 DOI: 10.1101/gad.240200.114

Date:

09-Apr-14 Release date: 14-May-14

Protein chains

P61964  (WDR5_HUMAN) -  WD repeat-containing protein 5 from Homo sapiens

Seq: 334 a.a.

Struc: 303 a.a.

Protein chains

Q7Z3B3  (KANL1_HUMAN) -  KAT8 regulatory NSL complex subunit 1 from Homo sapiens

Seq: 1105 a.a.

Struc: 14 a.a.*

* PDB and UniProt seqs differ at 1 residue position (black cross)

DOI no: 10.1101/gad.240200.114

Genes Dev 28:929-942 (2014)

PubMed id: 24788516

Structural analysis of the KANSL1/WDR5/KANSL2 complex reveals that WDR5 is required for efficient assembly and chromatin targeting of the NSL complex.

J.Dias, N.Van Nguyen, P.Georgiev, A.Gaub, J.Brettschneider, S.Cusack, J.Kadlec, A.Akhtar.

ABSTRACT

The subunits of the nonspecific lethal (NSL) complex, which include the histone acetyltransferase MOF (males absent on the first), play important roles in various cellular functions, including transcription regulation and stem cell identity maintenance and reprogramming, and are frequently misregulated in disease. Here, we provide the first biochemical and structural insights into the molecular architecture of this large multiprotein assembly. We identified several direct interactions within the complex and show that KANSL1 acts as a scaffold protein interacting with four other subunits, including WDR5, which in turn binds KANSL2. Structural analysis of the KANSL1/WDR5/KANSL2 subcomplex reveals how WDR5 is recruited into the NSL complex via conserved linear motifs of KANSL1 and KANSL2. Using structure-based KANSL1 mutants in transgenic flies, we show that the KANSL1-WDR5 interaction is required for proper assembly, efficient recruitment of the NSL complex to target promoters, and fly viability. Our data clearly show that the interactions of WDR5 with the MOF-containing NSL complex and MLL/COMPASS histone methyltransferase complexes are mutually exclusive. We propose that rather than being a shared subunit, WDR5 plays an important role in assembling distinct histone-modifying complexes with different epigenetic regulatory roles.