Background papers for a1/alpha2 Homeodomain Discussion

The primary papers (Li, T., Stark, M. R., Johnson, A. D., and Wolberger, C., 1995, "Crystal Structure of the MATa1/MATalpha2 Homeodomain Heterodimer Bound to DNA." Science 270, 262-269 and Jin, Y., Mead, J., Li, T., Wolberger, C., and Vershon, A. K. "Altered DNA Recognition and Bending by Insertions in the alpha2 Tail of the Yeast a1/alpha2 Homeodomain Heterodimer." pp. 290-293), to be discussed 3/6/96, present crystallographic and mutational studies on the recognition of DNA by this heterodimer and the concurrent folding of the C-terminal alpha2 helix. The papers below cover some related biochemical, structural, and genetic studies. We will be interested in how the crystal structure brought together a variety of disparate observations.

Background Area (paper)
NMR studies on alpha2 C-terminal helix folding (Phillips et al., 1994)
Homodimer vs. heterodimer binding affinity and specificity (Goutte and Johnson, 1993)
Biochemical work on protein orientation (Goutte and Johnson, 1994)
SRF (~MCM1) structure (Pellegrini et al., 1995)
Downstream repression (Herschbach et al., 1994)
Biochemical evidence for DNA bending in the complex (Smith et al., 1995)
Alternative dimerization possibilities (Ho et al., 1994)
Cooperativity in Paired domain homo- and heterodimers (Wilson et al., 1993)
Interaction between alpha2 and MCM1 on DNA (Smith and Johnson, 1992)

Goutte, C. and Johnson, A. D. (1993). "Yeast a1 and alpha2 Homeodomain Proteins Form a DNA-binding Activity with Properties Distinct from those of either Protein." J. Mol. Biol. 233, 359-371.

Goutte, C. and Johnson, A. D. (1994). "Recognition of a DNA operator by a dimer composed of two different homeodomain proteins." EMBO J. 13, 1434-1442.

Herschbach, B. M., Arnaud, M. B., and Johnson, A. D. (1994). "Transcriptional repression directed by the yeast alpha2 protein in vitro." Nature 370, 309-311.

Ho, C.-Y., Adamson, J. G., Hodges, R. S., and Smith, M. (1994). "Heterodimerization of the yeast MATa1 and MATalpha2 proteins is mediated by two leucine zipper-like coiled-coil motifs." EMBO J. 13, 1403-1413.

Pellegrini, L., Tan, S., and Richmond, T. J. (1995). "Structure of serum response factor core bound to DNA." Nature 376, 490-498.

Phillips, C. L., Stark, M. R., Johnson, A. D., and Dahlquist, F. W. (1994). "Heterodimerization of the Yeast Homeodomain Transcriptional Regulators alpha2 and a1 Induces an Interfacial Helix in alpha2." Biochemistry 33, 9294-9302.

Smith, D. L., Desai, A., and Johnson, A. D. (1995). "DNA bending by the a1 and alpha2 homeodomain proteins from yeast." Nucleic Acids Res. 23(7), 1239-1243.

Smith, D. L. and Johnson, A. D. (1992). "A Molecular Mechanism for Combinatorial Control in Yeast: MCM1 Protein Sets the Spacing and Orientation of the Homeodomains of an alpha2 Dimer." Cell 68, 133-142.

Wilson, D., Sheng, G., Lecuit, T., Dostatni, N., and Desplan, C. (1993). "Cooperative dimerization of Paired class homeo domains on DNA." Genes Dev. 7, 2120-2134.