THE SOLUTION STRUCTURE OF THE FIRST ZINC-FINGER DOMAIN OF SW15 - A NOVEL STRUCTURAL EXTENSION TO A COMMON FOLD

Background: The 2Cys-2His (C-2-H-2) zinc finger is a protein domain co mmonly used for sequence-specific DNA recognition. The zinc fingers of the yeast transcription factors SW15 and ACE2 share strong sequence h omology, which extends into a region N-terminal to the first finger, s uggesting that the DNA-binding domains of these two proteins include a dditional structural elements. Results: Structural analysis of the zin c fingers of SW15 reveals that a 15 residue region N-terminal to the f inger motifs forms part of the structure of the first finger domain, a dding a beta strand and a helix not previously observed in other zinc finger structures. Sequence analysis suggests that other zinc finger p roteins may also have this structure. Biochemical studies show that th is additional structure increases DNA-binding affinity. Conclusions: T he structural analysis presented reveals a novel zinc finger structure in which additional structural elements have been added to the C-2-H- 2 zinc finger fold. This additional structure may enhance stability an d has implications for DNA recognition by extending the potential DNA- binding surface of a single zinc finger domain.