TY - JOUR
AU - Pogenberg, Vivian
AU - Consani Textor, Larissa
AU - Vanhille, Laurent
AU - Holton, Simon J.
AU - Sieweke, Michael H.
AU - Wilmanns, Matthias
TI - Design of a bZip Transcription Factor with Homo/Heterodimer-Induced DNA-Binding Preference
JO - Structure
VL - 22
IS - 3
SN - 0969-2126
CY - London [u.a.]
PB - Elsevier Science
M1 - PUBDB-2015-01355
SP - 466 - 477
PY - 2014
N1 - © Elsevier Ltd. Open Archive
AB - The ability of basic leucine zipper transcription factors for homo- or heterodimerization provides a paradigm for combinatorial control of eukaryotic gene expression. It has been unclear, however, how facultative dimerization results in alternative DNA-binding repertoires on distinct regulatory elements. To unravel the molecular basis of such coupled preferences, we determined two high-resolution structures of the transcription factor MafB as a homodimer and as a heterodimer with c-Fos bound to variants of the Maf-recognition element. The structures revealed several unexpected and dimer-specific coiled-coil-heptad interactions. Based on these findings, we have engineered two MafB mutants with opposite dimerization preferences. One of them showed a strong preference for MafB/c-Fos heterodimerization and enabled selection of heterodimer-favoring over homodimer-specific Maf-recognition element variants. Our data provide a concept for transcription factor design to selectively activate dimer-specific pathways and binding repertoires.
LB - PUB:(DE-HGF)16
UR - <Go to ISI:>//WOS:000333025700012
C6 - pmid:24530283
DO - DOI:10.1016/j.str.2013.12.017
UR - https://bib-pubdb1.desy.de/record/207457
ER -