Structural Analysis of MED-1 Reveals Unexpected Diversity in the Mechanism of DNA Recognition by GATA-type Zinc

MED-1 is a member of a group of divergent GATA-type zinc finger proteins recently identified in several species ofCaenorh-abditis. The med genes are transcriptional regulators that are involved in the specification of the mesoderm and endoderm precursor cells in nematodes. Unlike other GATA-type zinc fin-gers that recognize the consensus sequence (A/C/T)GATA(A/ G), the MED-1 zinc finger (MED1zf) binds the larger and atypi-cal site GTATACT(T/C)3. We have examined the basis for this unusual DNA specificity using a range of biochemical and bio-physical approaches.Most strikingly, we show that although the core of the MED1zf structure is similar to that of GATA-1, the basic tail C-terminal to the zinc finger unexpectedly adopts an -helical structure upon binding DNA. This additional helix appears to contact the major groove of the DNA, making contacts that explain the extended DNA consensus sequence observed fo