Unknown

Dataset Information

0

Mechanism of conditional partner selectivity in MITF/TFE family transcription factors with a conserved coiled coil stammer motif.


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.

SUBMITTER: Pogenberg V 

PROVIDER: S-EPMC6954422 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

altmetric image

Publications

Mechanism of conditional partner selectivity in MITF/TFE family transcription factors with a conserved coiled coil stammer motif.

Pogenberg Vivian V   Ballesteros-Álvarez Josué J   Schober Romana R   Sigvaldadóttir Ingibjörg I   Obarska-Kosinska Agnieszka A   Milewski Morlin M   Schindl Rainer R   Ögmundsdóttir Margrét Helga MH   Steingrímsson Eiríkur E   Wilmanns Matthias M  

Nucleic acids research 20200101 2


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  ...[more]

Similar Datasets

| S-EPMC2896526 | biostudies-literature
| S-EPMC6500429 | biostudies-literature
| S-EPMC2749845 | biostudies-literature
| S-EPMC3932864 | biostudies-literature
| S-EPMC4069070 | biostudies-literature
| S-EPMC5447885 | biostudies-literature
| S-EPMC3384579 | biostudies-literature
| S-EPMC1920550 | biostudies-literature
| S-EPMC532435 | biostudies-literature
| S-EPMC419459 | biostudies-literature