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 i nteractions, In addition to self-association and DNA binding, MyoD ass ociates with a number of other HLH-containing proteins, thereby modula ting the strength and specificity of its DNA binding, Here, we examine the interactions of full-length MyoD with itself and with an HLH-cont aining peptide portion of an E2A gene product, E47-96. Analytical ultr acentrifugation reveals that MyoD forms micelles that contain more tha n 100 monomers and are asymmetric and stable up to 36 degrees C, The c ritical micelle concentration increases slightly with temperature, but micelle size is unaffected, The micelles are in reversible equilibriu m with monomer, Addition of E47-96 results in the stoichiometric forma tion of stable MyoD-E47-96 heterodimers and the depletion of micelles, Micelle formation effectively holds the concentration of free MyoD co nstant and equal to the critical micelle concentration, In the presenc e of micelles, the extent of all interactions involving free MyoD is i ndependent of the total MyoD concentration and independent of one anot her, For DNA binding, the apparent relative specificity for different sites can be affected. In general, heterodimer-associated activities w ill depend on the self-association behavior of the partner protein.