Abstract

It is known that the DNA binding Runt domain of the AML1/Runx1 transcription factor coordinates Cl − ions. In this paper we have determined Cl − binding affinities of AML1 by 35Cl nuclear magnetic resonance (NMR) linewidth analysis. The Runt domain binds Cl − with a dissociation constant ( K d,Cl) of 34 mM. If CBFβ is added to form a 1:1 complex, the K d,Cl value increases to 56 mM. Homology modeling suggests that a high occupancy Cl − binding site overlaps with the DNA binding surface. NMR data show that DNA displaces this Cl − ion. Possible biological roles of Cl − binding are discussed based on these findings.

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