Crystal Analysis Reveals Transcription Factor Binding Structure

A recent study on the myocyte enhancer factor-2 (MEF2) family of transcription factors describes the crystal structure of the MADS-box/MEF2S domain of human MEF2B bound to a motif of the transcriptional co-repressor Cabin1 and DNA at a resolution of 2.2 angstroms. The structure shows that differences in the protein-binding groove result in different types of MEF2.

The MEF2 family of transcription factors functions in the development and activity of T cells, neuronal cells, and muscle cells. MEF2 is capable of repressing or activating transcription by association with a variety of co-repressors or co-activators in a calcium-dependent manner. MEF2 has been implicated in general inflammation and heart hypertrophy, a condition characterized by enlargement of the heart.

The structure, determined by investigators at the University of Colorado (Boulder, USA) and John Hopkins University (Baltimore, MD, USA), revealed that the required helper proteins are bound in a groove in the top of MEF2. The study was published in the April 17, 2003, issue of Nature.

"Different types of cells have a different subset of four very similar versions of MEF2, each of which binds the same genes but different helper proteins,” explained contributing author Dr. Jun O. Liu, professor of pharmacology and neuroscience at Johns Hopkins. "Now we know that subtle differences in the protein-binding groove give each MEF2 its specificity, preventing a cell from carrying out inappropriate instructions. We do not know what effect blocking MEF2 would have, but we now know it is possible to try.”




Related Links:
University of Colorado
Johns Hopkins University