Chloride binding by the AML1/Runx1 transcription factor studied by NMR

M Wolf-Watz; S Bäckström; T Grundström; U Sauer; T Härd

doi:10.1016/s0014-5793(00)02390-5

Chloride binding by the AML1/Runx1 transcription factor studied by NMR

FEBS Lett. 2001 Jan 12;488(1-2):81-4. doi: 10.1016/s0014-5793(00)02390-5.

Authors

M Wolf-Watz¹, S Bäckström, T Grundström, U Sauer, T Härd

Affiliation

¹ Department of Biotechnology, Royal Institute of Technology, Center for Structural Biochemistry, Novum, Huddinge, Sweden.

PMID: 11163800
DOI: 10.1016/s0014-5793(00)02390-5

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 (35)Cl nuclear magnetic resonance (NMR) linewidth analysis. The Runt domain binds Cl(-) with a dissociation constant (K(d,Cl)) of 34 mM. If CBFbeta 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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Amino Acid Sequence
Binding, Competitive
Chlorides / antagonists & inhibitors
Chlorides / metabolism*
Core Binding Factor Alpha 2 Subunit
DNA / antagonists & inhibitors
DNA / metabolism
DNA-Binding Proteins / chemistry*
DNA-Binding Proteins / metabolism*
Magnetic Resonance Spectroscopy*
Models, Molecular
Molecular Sequence Data
Protein Binding
Protein Structure, Tertiary
Proto-Oncogene Proteins*
Sequence Alignment
Thermodynamics
Transcription Factor AP-2
Transcription Factors / chemistry*
Transcription Factors / metabolism*

Substances

Chlorides
Core Binding Factor Alpha 2 Subunit
DNA-Binding Proteins
Proto-Oncogene Proteins
Transcription Factor AP-2
Transcription Factors
DNA