ABSTRACT
The THAP (THanatos-Associated Protein) domain is an evolutionary conserved C2CH zinc-coordinating domain shared with a large family of cellular factors (THAP proteins). Many members of the THAP family act as transcription factors that control cell proliferation, cell cycle progression, angiogenesis, apoptosis and epigenetic gene silencing. They recognize specific DNA sequences in the promoters of target genes and subsequently recruit effector proteins. Recent structural and functional studies have allowed getting better insight into the nuclear and cellular functions of some THAP members and the molecular mechanisms by which they recognize DNA. The present article reviews recent advances in the knowledge of the THAP domains structures and their interaction with DNA, with a particular focus on NMR. It provides the solution structure of the THAP domain of THAP11, a recently characterized human THAP protein with important functions in transcription and cell growth in colon cancer.
Subject(s)
Apoptosis Regulatory Proteins/chemistry , DNA-Binding Proteins/chemistry , Nuclear Magnetic Resonance, Biomolecular , Nuclear Proteins/chemistry , Protein Interaction Domains and Motifs , Repressor Proteins/chemistry , Amino Acid Sequence , Animals , DNA-Binding Proteins/metabolism , DNA-Binding Proteins/physiology , Humans , Models, Biological , Models, Molecular , Molecular Sequence Data , Nuclear Magnetic Resonance, Biomolecular/methods , Protein Interaction Domains and Motifs/physiology , Repressor Proteins/metabolism , Repressor Proteins/physiology , Sequence Homology, Amino AcidABSTRACT
The reactive oxygen species H2O2 promotes the Zn7-metallothionein-3 induced Aß(40) aggregation of fibrillar type structures via slow cysteine oxidation and Zn(2+) release, whereas amorphous aggregates are formed by addition of Zn(2+) to Aß(40).