6FX5

MITF dimerization mutant

Summary for 6FX5

• Entry DOI: 10.2210/pdb6fx5/pdb
• Descriptor: Microphthalmia-associated transcription factor, SULFATE ION (3 entities in total)
• Functional Keywords: melanocytes, bhlhzip, autophagy, transcription
• Biological source: Mus musculus (Mouse)
• Total number of polymer chains: 2
• Total formula weight: 19068.01

Authors

Pogenberg, V.,Milewski, M.,Wilmanns, M. (deposition date: 2018-03-08, release date: 2019-03-20, Last modification date: 2024-01-17)

Primary citation

Pogenberg, V.,Ballesteros-Alvarez, J.,Schober, R.,Sigvaldadottir, I.,Obarska-Kosinska, A.,Milewski, M.,Schindl, R.,Ogmundsdottir, M.H.,Steingrimsson, E.,Wilmanns, M.
Mechanism of conditional partner selectivity in MITF/TFE family transcription factors with a conserved coiled coil stammer motif.
Nucleic Acids Res., 48:934-948, 2020

PubMed 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.

PubMed: 31777941
DOI: 10.1093/nar/gkz1104

Experimental method

X-RAY DIFFRACTION (2.05 Å)