Structural highlights
Disease
[ZBT16_HUMAN] Defects in ZBTB16 are the cause of skeletal defects genital hypoplasia and mental retardation (SGYMR) [MIM:612447]. A disorder characterized by mental retardation, craniofacial dysmorphism, microcephaly and short stature. Additional features include absence of the thumbs, hypoplasia of the radii and ulnae, additional vertebrae and ribs, retarded bone age and genital hypoplasia.[1] Note=A chromosomal aberration involving ZBTB16 may be a cause of acute promyelocytic leukemia (APL). Translocation t(11;17)(q32;q21) with RARA.
Function
[ZBT16_HUMAN] Probable transcription factor. May play a role in myeloid maturation and in the development and/or maintenance of other differentiated tissues. Probable substrate-recognition component of an E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins.[2]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
The evolutionarily conserved BTB/POZ domain from the promyelocytic leukemia zinc finger (PLZF) oncoprotein mediates transcriptional repression through the recruitment of corepressor proteins containing histone deacetylases in acute promyelocytic leukemia. We have determined the 2.0 A crystal structure of the BTB/POZ domain from PLZF (PLZF-BTB/POZ), and have carried out biochemical analysis of PLZF-BTB/POZ harboring site-directed mutations to probe structure-function relationships. The structure reveals a novel alpha/beta homodimeric fold in which dimer interactions occur along two surfaces of the protein subunits. The conservation of BTB/POZ domain residues at the core of the protomers and at the dimer interface implies an analogous fold and dimerization mode for BTB/POZ domains from otherwise functionally unrelated proteins. Unexpectedly, the BTB/POZ domain forms dimer-dimer interactions in the crystals, suggesting a mode for higher-order protein oligomerization for BTB/POZ-mediated transcriptional repression. Biochemical characterization of PLZF-BTB/POZ harboring mutations in conserved residues involved in protein dimerization reveals that the integrity of the dimer interface is exquisitely sensitive to mutation and that dimer formation is required for wild-type levels of transcriptional repression. Interestingly, similar mutational analysis of residues within a pronounced protein cleft along the dimer interface, which had been implicated previously for interaction with corepressors, has negligible effects on dimerization or transcriptional repression. Together, these studies form a structure-function framework for understanding BTB/POZ-mediated oligomerization and transcriptional repression properties.
Structure-function studies of the BTB/POZ transcriptional repression domain from the promyelocytic leukemia zinc finger oncoprotein.,Li X, Peng H, Schultz DC, Lopez-Guisa JM, Rauscher FJ 3rd, Marmorstein R Cancer Res. 1999 Oct 15;59(20):5275-82. PMID:10537309[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Fischer S, Kohlhase J, Bohm D, Schweiger B, Hoffmann D, Heitmann M, Horsthemke B, Wieczorek D. Biallelic loss of function of the promyelocytic leukaemia zinc finger (PLZF) gene causes severe skeletal defects and genital hypoplasia. J Med Genet. 2008 Nov;45(11):731-7. doi: 10.1136/jmg.2008.059451. Epub 2008 Jul, 8. PMID:18611983 doi:10.1136/jmg.2008.059451
- ↑ Furukawa M, He YJ, Borchers C, Xiong Y. Targeting of protein ubiquitination by BTB-Cullin 3-Roc1 ubiquitin ligases. Nat Cell Biol. 2003 Nov;5(11):1001-7. Epub 2003 Oct 5. PMID:14528312 doi:10.1038/ncb1056
- ↑ Li X, Peng H, Schultz DC, Lopez-Guisa JM, Rauscher FJ 3rd, Marmorstein R. Structure-function studies of the BTB/POZ transcriptional repression domain from the promyelocytic leukemia zinc finger oncoprotein. Cancer Res. 1999 Oct 15;59(20):5275-82. PMID:10537309
