Structure and Backbone Dynamics of Apo-CBF in Solution
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- 作者：Magnus Wolf-Watz ; Thomas Grundströ ; m ; and Torleif Hä ; rd
- 刊名：Biochemistry
- 出版年：2001
- 出版时间：September 25, 2001
- 年：2001
- 卷：40
- 期：38
- 页码：11423 - 11432
- 全文大小：361K
- 年卷期：v.40,no.38(September 25, 2001)
- ISSN：1520-4995
文摘
Runx proteins constitute a family of mammalian transcription factors that interact with DNAthrough their evolutionarily conserved Runt domain. CBF
, alternatively denoted PEBP2, is the non-DNA-binding heterodimer partner and acts to enhance the DNA binding affinity of Runx proteins. Runxproteins and CBF are associated with a variety of biological functions and human diseases; they are, forexample, together the most frequent targets for chromosomal rearrangements in acute human leukemias.We have determined the solution structure and characterized the backbone dynamics of C-terminallytruncated fragments containing residues 1-141 of CBF. The present apo-CBF structure is very similarto that seen in a Runt-CBF complex. An evaluation of backbone 15N NMR relaxation parameters showsthat CBF is a rigid molecule with high order parameters throughout the backbone; the only regionsdisplaying significant dynamics are a long loop and the C-terminal 
-helix. A few residues display relaxationbehavior indicating conformational exchange on microsecond to millisecond time scales, but only one ofthese is located at the Runt binding surface. Our structure and dynamics analysis of CBF thereforesuggests that the protein binds to Runt without large conformational changes or induced folding ("lock-and-key" interaction). The apo-CBF structure presented here exhibits several significant differences withtwo other published NMR ensembles of very similar protein fragments. The differences are located infour regions outside of the central -barrel, whereas the -barrel itself is almost identical in the threeNMR structures. The comparison illustrates that independently determined NMR structures may displayrather large differences in backbone conformation in regions that appear to be well-defined in each of thecalculated NMR ensembles.
, alternatively denoted PEBP2, is the non-DNA-binding heterodimer partner and acts to enhance the DNA binding affinity of Runx proteins. Runxproteins and CBF are associated with a variety of biological functions and human diseases; they are, forexample, together the most frequent targets for chromosomal rearrangements in acute human leukemias.We have determined the solution structure and characterized the backbone dynamics of C-terminallytruncated fragments containing residues 1-141 of CBF. The present apo-CBF structure is very similarto that seen in a Runt-CBF complex. An evaluation of backbone 15N NMR relaxation parameters showsthat CBF is a rigid molecule with high order parameters throughout the backbone; the only regionsdisplaying significant dynamics are a long loop and the C-terminal -helix. A few residues display relaxationbehavior indicating conformational exchange on microsecond to millisecond time scales, but only one ofthese is located at the Runt binding surface. Our structure and dynamics analysis of CBF thereforesuggests that the protein binds to Runt without large conformational changes or induced folding ("lock-and-key" interaction). The apo-CBF structure presented here exhibits several significant differences withtwo other published NMR ensembles of very similar protein fragments. The differences are located infour regions outside of the central -barrel, whereas the -barrel itself is almost identical in the threeNMR structures. The comparison illustrates that independently determined NMR structures may displayrather large differences in backbone conformation in regions that appear to be well-defined in each of thecalculated NMR ensembles.