| Structural highlights
Function
[ABDB_DROME] Sequence-specific transcription factor which is part of a developmental regulatory system that provides cells with specific positional identities on the anterior-posterior axis. [EXD_DROME] Transcription factor which acts with the selector homeodomain proteins altering the regulation of downstream target genes such as wingless (wg), teashirt (tsh) and decapentaplegic (dpp), thus affecting segmental identity. Delimits the eye field and prevent inappropriate eye development. Required for proper localization of chordotonal organs within the peripheral nervous system.[1] [2] [3] [4] [5] [6]
Publication Abstract from PubMed
Transcription factors bind to their binding sites over a wide range of affinities, yet how differences in affinity are encoded in DNA sequences is not well understood. Here, we report X-ray crystal structures of four heterodimers of the Hox protein AbdominalB bound with its cofactor Extradenticle to four target DNA molecules that differ in affinity by up to approximately 20-fold. Remarkably, despite large differences in affinity, the overall structures are very similar in all four complexes. In contrast, the predicted shapes of the DNA binding sites (i.e., the intrinsic DNA shape) in the absence of bound protein are strikingly different from each other and correlate with affinity: binding sites that must change conformations upon protein binding have lower affinities than binding sites that have more optimal conformations prior to binding. Together, these observations suggest that intrinsic differences in DNA shape provide a robust mechanism for modulating affinity without affecting other protein-DNA interactions.
Intrinsic DNA Shape Accounts for Affinity Differences between Hox-Cofactor Binding Sites.,Zeiske T, Baburajendran N, Kaczynska A, Brasch J, Palmer AG 3rd, Shapiro L, Honig B, Mann RS Cell Rep. 2018 Aug 28;24(9):2221-2230. doi: 10.1016/j.celrep.2018.07.100. PMID:30157419[7]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Rauskolb C, Peifer M, Wieschaus E. extradenticle, a regulator of homeotic gene activity, is a homolog of the homeobox-containing human proto-oncogene pbx1. Cell. 1993 Sep 24;74(6):1101-12. PMID:8104703
- ↑ Flegel WA, Singson AW, Margolis JS, Bang AG, Posakony JW, Murre C. Dpbx, a new homeobox gene closely related to the human proto-oncogene pbx1 molecular structure and developmental expression. Mech Dev. 1993 May;41(2-3):155-61. PMID:8100142
- ↑ Rauskolb C, Wieschaus E. Coordinate regulation of downstream genes by extradenticle and the homeotic selector proteins. EMBO J. 1994 Aug 1;13(15):3561-9. PMID:7914871
- ↑ Rieckhof GE, Casares F, Ryoo HD, Abu-Shaar M, Mann RS. Nuclear translocation of extradenticle requires homothorax, which encodes an extradenticle-related homeodomain protein. Cell. 1997 Oct 17;91(2):171-83. PMID:9346235
- ↑ Kurant E, Pai CY, Sharf R, Halachmi N, Sun YH, Salzberg A. Dorsotonals/homothorax, the Drosophila homologue of meis1, interacts with extradenticle in patterning of the embryonic PNS. Development. 1998 Mar;125(6):1037-48. PMID:9463350
- ↑ Pai CY, Kuo TS, Jaw TJ, Kurant E, Chen CT, Bessarab DA, Salzberg A, Sun YH. The Homothorax homeoprotein activates the nuclear localization of another homeoprotein, extradenticle, and suppresses eye development in Drosophila. Genes Dev. 1998 Feb 1;12(3):435-46. PMID:9450936
- ↑ Zeiske T, Baburajendran N, Kaczynska A, Brasch J, Palmer AG 3rd, Shapiro L, Honig B, Mann RS. Intrinsic DNA Shape Accounts for Affinity Differences between Hox-Cofactor Binding Sites. Cell Rep. 2018 Aug 28;24(9):2221-2230. doi: 10.1016/j.celrep.2018.07.100. PMID:30157419 doi:https://dx.doi.org/10.1016/j.celrep.2018.07.100
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