The CENPB-type HTH domain is a DNA-binding, helix-turn-helix (HTH) domain of about 70-75 amino acids, present in eukaryotic centromere proteins and transposases. The domain is named after the mammalian major centromere autoantigen B or centromere protein B (CENP-B), which is a fundamental centromere component of chromosomes. The N terminus of CENP-B contains two DNA-binding HTH domains, which bind to adjacent major grooves of DNA. The N terminus of CENP-B is formed by a psq-type HTH domain and C-terminal to this domain lies the CENPB-type HTH domain. These two HTH domains together bind specifically to a 17-base-pair sequence, the CENP-B box, which occurs in alpha-satellite DNA in human centromeres [ (PUBMED:16183641) ].
The structure of the CENPB-type HTH domain is composed of three alpha-helices. The second and third helices connected via a turn comprise the helix-turn-helix motif. Helix 3 is termed the recognition helix as it binds the DNA major groove, like in other HTHs. In CENP-B this domain recognises site 3 of the CENP-B box, while the preceding psq-type HTH binds site 1 of the CENP-B box, and a connecting linker loop binds in the minor groove of DNA and recognises site 2 [ (PUBMED:11726497) ].
Some proteins known to contain a CENPB-type HTH domain:
Mammalian centromere protein B (CENP-B), associated with the centromere and specifically binding DNA to the CENP-B box.
Mammalian jerky protein, involved in epileptic seizures in mice [ (PUBMED:15487591) ].
Fission yeast ARS-binding protein 1 (abp1) [ (PUBMED:17112379) ] and CENP-B homologue proteins (CBHP-1 and 2), which are centromere proteins [ (PUBMED:9237993) (PUBMED:11238404) ].
Epileptic seizures caused by inactivation of a novel gene, jerky, relatedto centromere binding protein-B in transgenic mice.
Nat Genet. 1995; 11: 71-5
Display abstract
Epidemiological data and genetic studies indicate that certain forms ofhuman epilepsy are inherited. Based on the similarity between the humanand mouse genomes, mouse models of epilepsy could facilitate the discoveryof genes associated with epilepsy syndromes. Here, we report aninsertional murine mutation that inactivates a novel gene and results inwhole body jerks, generalized clonic seizures, and epileptic brainactivity in transgenic mice. The gene, named jerky, encodes a putative41.7 kD protein displaying homology to a number of nuclear regulatoryproteins, suggesting that perhaps the jerky protein is able to bind DNA.
An ancient family of embryonically expressed mouse genes sharing a conserved protein motif with the T locus.
Nat Genet. 1994; 7: 383-9
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The T locus encodes a product with DNA binding activity that is likely to play a role in the development of all vertebrate organisms. We have identified and characterized a novel family of mouse genes that share a protein motif, the T-box, with the prototypical T locus. The T-box domain of the T locus co-localizes with its DNA binding activity. Each T-box gene is expressed in a unique temporal and spatial pattern during embryogenesis. Phylogenetic analysis suggests that at least three T-box genes were present in the common ancestor to vertebrates and invertebrates. Thus, members of the T-box family could have played a role in the evolution of all metazoan organisms.
A human centromere protein, CENP-B, has a DNA binding domain containingfour potential alpha helices at the NH2 terminus, which is separable fromdimerizing activity.
J Cell Biol. 1992; 119: 1413-27
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The alphoid DNA-CENP-B (centromere protein B) complex is the firstsequence-specific DNA/protein complex detected in the centromeric regionof human chromosomes. In the reaction, CENP-B recognizes a 17-bp sequence(CENP-B box) and assembles two alphoid DNA molecules into a complex, whichis designated complex A (Muro, Y., H. Masumoto, K. Yoda, N. Nozaki, M.Ohashi, and T. Okazaki. 1992. J. Cell Biol. 116:585-596). Since CENP-Bgene is conserved in mammalian species and CENP-B boxes are found also inmouse centromere satellite DNA (minor satellite), this sequence-specificDNA-protein interaction may be important for some kind of commoncentromere function. In this study we have characterized the structure ofCENP-B and CENP-B-alphoid DNA complex. We have shown by chemicalcross-linking that CENP-B formed a dimer, and have estimated by molecularweight determination the composition of complex A to be a CENP-B dimer andtwo molecules of alphoid DNA. The DNA binding domain has been delimitedwithin the NH2-terminal 125-amino acid region containing four potentialalpha-helices using truncated CENP-B made in Escherichia coli cells. Wehave shown that CENP-B had sites highly sensitive to proteases and thatthe DNA binding domain was separable from the dimerizing activity by theproteolytic cleavage at 20 kD from the COOH terminus of the molecule.Thus, CENP-B may organize a higher order structure in the centromere byjuxtaposing two CENP-B boxes in the alphoid DNA repeat through both theDNA-protein and protein-protein interactions.
