3vd0
structure of p73 DNA binding domain tetramer modulates p73 transactivationstructure of p73 DNA binding domain tetramer modulates p73 transactivation
Structural highlights
Publication Abstract from PubMedThe transcription factor p73 triggers developmental pathways and overlaps stress-induced p53 transcriptional pathways. How p53-family response elements determine and regulate transcriptional specificity remains an unsolved problem. In this work, we have determined the first crystal structures of p73 DNA-binding domain tetramer bound to response elements with spacers of different length. The structure and function of the adaptable tetramer are determined by the distance between two half-sites. The structures with zero and one base-pair spacers show compact p73 DNA-binding domain tetramers with large tetramerization interfaces; a two base-pair spacer results in DNA unwinding and a smaller tetramerization interface, whereas a four base-pair spacer hinders tetramerization. Functionally, p73 is more sensitive to spacer length than p53, with one base-pair spacer reducing 90% of transactivation activity and longer spacers reducing transactivation to basal levels. Our results establish the quaternary structure of the p73 DNA-binding domain required as a scaffold to promote transactivation. Structure of p73 DNA-binding domain tetramer modulates p73 transactivation.,Ethayathulla AS, Tse PW, Monti P, Nguyen S, Inga A, Fronza G, Viadiu H Proc Natl Acad Sci U S A. 2012 Apr 2. PMID:22474346[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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