Mechanism of conditional partner selectivity in MITF/TFE family transcription factors with a conserved coiled coil stammer motif
| Autor: | Vivian Pogenberg, Margret H. Ogmundsdottir, Romana Schober, Morlin Milewski, Agnieszka Obarska-Kosinska, Rainer Schindl, Josué Ballesteros-Álvarez, Matthias Wilmanns, Ingibjörg Sigvaldadóttir, Eiríkur Steingrímsson |
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| Rok vydání: | 2019 |
| Předmět: |
Leucine zipper
Protein Conformation Plasma protein binding Biology Ligands Mice 03 medical and health sciences Protein structure Protein Domains Structural Biology Transcription (biology) Genetics Animals Transcription factor 030304 developmental biology Cell Nucleus Coiled coil Microphthalmia-Associated Transcription Factor 0303 health sciences integumentary system Basic Helix-Loop-Helix Leucine Zipper Transcription Factors 030302 biochemistry & molecular biology Microphthalmia-associated transcription factor Cell biology Protein Multimerization Nuclear localization sequence Protein Binding |
| Zdroj: | 'Nucleic Acids Research ', vol: 48, pages: 934-948 (2020) Nucleic Acids Research |
| ISSN: | 1362-4962 0305-1048 |
| DOI: | 10.1093/nar/gkz1104 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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