1ean

File:1ean.gif

spinqualitylabelsall models 1ean, resolution 1.70Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

THE RUNX1 RUNT DOMAIN AT 1.25A RESOLUTION: A STRUCTURAL SWITCH AND SPECIFICALLY BOUND CHLORIDE IONS MODULATE DNA BINDING

OverviewOverview

The evolutionarily conserved Runt homology domain is characteristic of the, RUNX family of heterodimeric eukaryotic transcription factors, including, RUNX1, RUNX2 and RUNX3. The genes for RUNX1, also termed acute myeloid, leukemia protein 1, AML1, and its dimerization partner core-binding factor, beta, CBFbeta, are essential for hematopoietic development and are, together the most common targets for gene rearrangements in acute human, leukemias. Here, we describe the crystal structure of the uncomplexed, RUNX1 Runt domain at 1.25A resolution and compare its conformation to, previously published structures in complex with DNA, CBFbeta or both. We, find that complex formation induces significant structural rearrangements, in this immunoglobulin (Ig)-like DNA-binding domain. Most pronounced is, the movement of loop L11, which changes from a closed conformation in the, free Runt structure to an open conformation in the CBFbeta-bound and, DNA-bound forms. This transition, which we refer to as the S-switch, and, accompanying structural movements that affect other parts of the Runt, domain are crucial for sustained DNA binding. The closed to open, transition can be induced by CBFbeta alone; suggesting that one role of, CBFbeta is to trigger the S-switch and to stabilize the Runt domain in a, conformation enhanced for DNA binding.A feature of the Runt domain, hitherto unobserved in any Ig-like DNA-binding domain is the presence of, two specifically bound chloride ions. One chloride ion is coordinated by, amino acid residues that make direct DNA contact. In a series of, electrophoretic mobility-shift analyses, we demonstrate a chloride ion, concentration-dependent stimulation of the DNA-binding activity of Runt in, the physiological range. A comparable DNA-binding stimulation was observed, for negatively charged amino acid residues. This suggests a regulatory, mechanism of RUNX proteins through acidic amino acid residues provided by, activation domains during cooperative interaction with other transcription, factors.

About this StructureAbout this Structure

1EAN is a Single protein structure of sequence from Mus musculus with CL as ligand. Structure known Active Site: CL1. Full crystallographic information is available from OCA.

ReferenceReference

The RUNX1 Runt domain at 1.25A resolution: a structural switch and specifically bound chloride ions modulate DNA binding., Backstrom S, Wolf-Watz M, Grundstrom C, Hard T, Grundstrom T, Sauer UH, J Mol Biol. 2002 Sep 13;322(2):259-72. PMID:12217689

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