MyoD forms micelles which can dissociate to form heterodimers with E47: implications of micellization on function.
MyoD is a member of a family of DNA-binding transcription factors that contain a helix-loop-helix (HLH) region involved in protein-protein interactions. In addition to self-association and DNA binding, MyoD associates with a number of other HLH-containing proteins, thereby modulating the strength and specificity of its DNA binding. Here, we examine the interactions of full-length MyoD with itself and with an HLH-containing peptide portion of an E2A gene product, E47-96. Analytical ultracentrifugation reveals that MyoD forms micelles that contain more than 100 monomers and are asymmetric and stable up to 36 degrees C. The critical micelle concentration increases slightly with temperature, but micelle size is unaffected. The micelles are in reversible equilibrium with monomer. Addition of E47-96 results in the stoichiometric formation of stable MyoD-E47-96 heterodimers and the depletion of micelles. Micelle formation effectively holds the concentration of free MyoD constant and equal to the critical micelle concentration. In the presence of micelles, the extent of all interactions involving free MyoD is independent of the total MyoD concentration and independent of one another. For DNA binding, the apparent relative specificity for different sites can be affected. In general, heterodimer-associated activities will depend on the self-association behavior of the partner protein.
Laue
T M
TM
Department of Biochemistry and Molecular Biology, University of New Hampshire, Durham 03824-3544, USA.
Starovasnik
M A
MA
Weintraub
H
H
Sun
X H
XH
Snider
L
L
Klevit
R E
RE
D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000378:metabolism; D018257:Helix-Loop-Helix Motifs; D008823:Micelles; D008956:Models, Chemical; D017570:MyoD Protein / Q000737:chemistry* / Q000378:metabolism; D011485:Protein Binding; D011487:Protein Conformation; D051820:TCF Transcription Factors; D058125:Transcription Factor 7-Like 1 Protein; D014157:Transcription Factors; D014461:Ultracentrifugation
D004268:DNA-Binding Proteins; D008823:Micelles; D017570:MyoD Protein; D051820:TCF Transcription Factors; D058125:Transcription Factor 7-Like 1 Protein; D014157:Transcription Factors