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Solution structure of the PHD domain from the KAP‐1 corepressor: structural determinants for PHD, RING and LIM zinc‐binding domains
Author(s) -
Capili Allan D.,
Schultz David C.,
Rauscher Frank J.,
Borden Katherine L.B.
Publication year - 2001
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/20.1.165
Subject(s) - corepressor , biology , zinc finger , lim domain , zinc , ring finger domain , domain (mathematical analysis) , ring (chemistry) , repressor , plasma protein binding , microbiology and biotechnology , biochemistry , transcription factor , gene , materials science , mathematical analysis , chemistry , mathematics , organic chemistry , metallurgy
Plant homeodomain (PHD) domains are found in >400 eukaryotic proteins, many of which are transcriptional regulators. Naturally occurring point mutations or deletions of this domain contribute to a variety of human diseases, including ATRX syndrome, myeloid leukemias and autoimmune dysfunction. Here we report the first structural characterization of a PHD domain. Our studies reveal that the PHD domain from KAP‐1 corepressor binds zinc in a cross‐brace topology between anti‐parallel β‐strands reminiscent of RING (really interesting new gene) domains. Using a mutational analysis, we define the structural features required for transcriptional repression by KAP‐1 and explain naturally occurring, disease‐causing mutations in PHD domains of other proteins. From a comparison of this PHD structure with previously reported RING and LIM (Lin11/Isl‐1/Mec‐3) structures, we infer sequence determinants that allow discrimination among PHD, RING and LIM motifs.