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PDBsum entry 4cy3
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Transcription
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PDB id
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4cy3
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References listed in PDB file
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Key reference
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Title
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Structural analysis of the kansl1/wdr5/kansl2 complex reveals that wdr5 is required for efficient assembly and chromatin targeting of the nsl complex.
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Authors
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J.Dias,
N.Van nguyen,
P.Georgiev,
A.Gaub,
J.Brettschneider,
S.Cusack,
J.Kadlec,
A.Akhtar.
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Ref.
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Genes Dev, 2014,
28,
929-942.
[DOI no: ]
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PubMed id
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Abstract
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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.
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