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SHR Neuro Cancer Cardio Lipid Metab Microb

Pogenberg, V; Ballesteros-Álvarez, J; Schober, R; Sigvaldadóttir, I; Obarska-Kosinska, A; Milewski, M; Schindl, R; Ögmundsdóttir, MH; Steingrímsson, E; Wilmanns, M.
Mechanism of conditional partner selectivity in MITF/TFE family transcription factors with a conserved coiled coil stammer motif.
Nucleic Acids Res. 2020; 48(2):934-948 Doi: 10.1093/nar/gkz1104 [OPEN ACCESS]
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Co-authors Med Uni Graz: Schindl Rainer; Schober Romana
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Abstract:: Interrupted dimeric coiled coil segments are found in a broad range of proteins and generally confer selective functional properties such as binding to specific ligands. However, there is only one documented case of a basic-helix-loop-helix leucine zipper transcription factor-microphthalmia-associated transcription factor (MITF)-in which an insertion of a three-residue stammer serves as a determinant of conditional partner selectivity. To unravel the molecular principles of this selectivity, we have analyzed the high-resolution structures of stammer-containing MITF and an engineered stammer-less MITF variant, which comprises an uninterrupted symmetric coiled coil. Despite this fundamental difference, both MITF structures reveal identical flanking in-phase coiled coil arrangements, gained by helical over-winding and local asymmetry in wild-type MITF across the stammer region. These conserved structural properties allow the maintenance of a proper functional readout in terms of nuclear localization and binding to specific DNA-response motifs regardless of the presence of the stammer. By contrast, MITF heterodimer formation with other bHLH-Zip transcription factors is only permissive when both factors contain either the same type of inserted stammer or no insert. Our data illustrate a unique principle of conditional partner selectivity within the wide arsenal of transcription factors with specific partner-dependent functional readouts. © The Author(s) 2019. Published by Oxford University Press on behalf of Nucleic Acids Research.
Find related publications in this database (using NLM MeSH Indexing): Animals -; Basic Helix-Loop-Helix Leucine Zipper Transcription Factors - chemistry; Basic Helix-Loop-Helix Leucine Zipper Transcription Factors - genetics; Cell Nucleus - chemistry; Ligands -; Mice -; Microphthalmia-Associated Transcription Factor - chemistry; Microphthalmia-Associated Transcription Factor - genetics; Protein Binding -; Protein Conformation -; Protein Domains - genetics; Protein Multimerization -