THE X-RAY STRUCTURE OF AN ATYPICAL HOMEODOMAIN PRESENT IN THE RAT-LIVER TRANSCRIPTION FACTOR LFB1 HNF1 AND IMPLICATIONS FOR DNA-BINDING

The transcription factor LFB1/HNF1 from rat liver nuclei is a 628 amin o acid protein that functions as a dimer binding to the inverted palin drome GTTAATNATTAAC consensus site. We have crystallized a 99 residue protein containing the homeodomain portion of LFB1, and solved its str ucture using X-ray diffraction data to 2.8 angstrom resolution. The to pology and orientation of the helices is essentially the same as that found in the engrailed, MATalpha2 and Antennapedia homeodomains, even though the LFB1 homeodomain contains 21 more residues. The 21 residue insertion is found in an extension of helix 2 and consequent lengtheni ng of the connecting loop between helix 2 and helix 3. Comparison with the engrailed homeodomain - DNA complex indicates that the mode of in teraction with DNA is similar in both proteins, with a number of conse rved contacts in the major groove. The extra 21 residues of the LFB1 h omeodomain are not involved in DNA binding. Binding of the LFB1 dimer to a B-DNA palindromic consensus sequence requires either a conformati onal change of the DNA (presumably bending), or a rearrangement of the subunits relative to the DNA.