Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0262471 (ENT)
 5,307 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

EMSY is a large nuclear protein that binds to the transactivation domain of BRCA2. EMSY contains an approximately 100-residue segment at the amino terminus called the ENT (EMSY N-terminal) domain. Plant proteins containing ENT domains also contain members of the royal family of chromatin-remodelling domains. It has been proposed that EMSY may have a role in chromatin-related processes. This is supported by the observation that a number of chromatin-regulator proteins, including HP1beta and BS69, bind directly to EMSY by means of a conserved motif adjacent to the ENT domain. Here, we report the crystal structure of residues 1-108 of EMSY at 2.0 A resolution. The structure contains both the ENT domain and the HP1beta/BS69-binding motif. This binding motif forms an extended peptide-like conformation that adopts distinct orientations in each subunit of the dimer. Biophysical and nuclear magnetic resonance analyses show that the main complex formed by EMSY and the chromoshadow domain of HP1 (HP1-CSD) consists of one EMSY dimer sandwiched between two HP1-CSD dimers. The HP1beta-binding motif is necessary and sufficient for EMSY to bind to the chromoshadow domain of HP1beta.
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PMID:Binding of EMSY to HP1beta: implications for recruitment of HP1beta and BS69. 1594 84

EMSY is a recently discovered gene encoding a BRCA2-associated protein and is amplified in some sporadic breast and ovarian cancers. The EMSY sequence contains no known domain except for a conserved approximately 100 residue segment at the N terminus. This so-called ENT domain is unique in the human genome, although multiple copies are found in Arabidopsis proteins containing members of the Royal family of chromatin remodelling domains. Here, we report the crystal structure of the ENT domain of EMSY, consisting of a unique arrangement of five alpha-helices that fold into a helical bundle arrangement. The fold shares regions of structural homology with the DNA-binding domain of homeodomain proteins. The ENT domain forms a homodimer via the anti-parallel packing of the extended N-terminal alpha-helix of each molecule. It is stabilized mainly by hydrophobic residues at the dimer interface and has a dissociation constant in the low micromolar range. The dimerisation of EMSY mediated by the ENT domain could provide flexibility for it to bind two or more different substrates simultaneously.
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PMID:Crystal structure of the ENT domain of human EMSY. 1597 17