Structure and functional analysis of the MYND domain.

The MYND domain (named after myeloid translocation protein 8, Nervy, and DEAF-1) is a conserved zinc binding domain. It is defined by seven conserved cysteine residues and a single histidine residue that are arranged in a C4-C2HC consensus. MYND domains exist in a large number of proteins that play important roles in development or are associated with cancers and have been shown to mediate protein-protein interactions, mainly in the context of transcriptional regulation. We have determined the three-dimensional structure of the MYND domain from human deformed epidermal autoregulatory factor-1 (DEAF-1). The structure reveals a novel zinc binding fold, in which the C4-C2HC motif forms two sequential zinc binding sites. The first and second zinc binding modules comprise a small beta hairpin and two short alpha helices, respectively. The sequential topology of the two zinc binding sites is distinct from the cross-brace PHD and RING finger folds but has some resemblance to LIM domains. The structure reveals that the MYND domain is a novel member of the treble-clef family of zinc binding domains. The MYND domains of BS69 and BOP bind ligands comprising a PXLXP peptide motif. On the basis of the solution structure of the DEAF-1 MYND domain we calculated a homology model of the MYND domain of the BS69 tumor suppressor. A mutational analysis of the BS69 MYND domain indicates that positively charged residues located on one face of its MYND domain are crucial for the molecular interactions of BS69. Different binding specificities of MYND domains may depend on distinct surface charge distributions.