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@ARTICLE{Pogenberg:139945,
author = {Pogenberg, V. and Oegmundsdottir, M. H. and
Bergsteinsdottir, K. and Schepsky, A. and Phung, B. and
Deineko, V. and Milewski, M. and Steingrimsson, E. and
Wilmanns, M. and DESY},
title = {{R}estricted leucine zipper dimerization and specificity of
{DNA} recognition of the melanocyte master regulator {MITF}},
journal = {Genes $\&$ development},
volume = {26},
issn = {0890-9369},
address = {Stanford, Calif.},
publisher = {HighWire Press},
reportid = {PHPPUBDB-24647},
pages = {2647-2658},
year = {2012},
note = {(c) Cold Spring Harbor Laboratory Press},
abstract = {Microphthalmia-associated transcription factor (MITF) is a
master regulator of melanocyte development and an important
oncogene in melanoma. MITF heterodimeric assembly with
related basic helix-loop-helix leucine zipper transcription
factors is highly restricted, and its binding profile to
cognate DNA sequences is distinct. Here, we determined the
crystal structure of MITF in its apo conformation and in the
presence of two related DNA response elements, the E-box and
M-box. In addition, we investigated mouse and human Mitf
mutations to dissect the functional significance of
structural features. Owing to an unusual three-residue shift
in the leucine zipper register, the MITF homodimer shows a
marked kink in one of the two zipper helices to allow an
out-of-register assembly. Removal of this insertion relieves
restricted heterodimerization by MITF and permits assembly
with the transcription factor MAX. Binding of MITF to the
M-box motif is mediated by an unusual nonpolar interaction
by Ile212, a residue that is mutated in mice and humans with
Waardenburg syndrome. As several related transcription
factors have low affinity for the M-box sequence, our
analysis unravels how these proteins discriminate between
similar target sequences. Our data provide a rational basis
for targeting MITF in the treatment of important hereditary
diseases and cancer.},
keywords = {Amino Acid Sequence / Animals / DNA-Binding Proteins:
chemistry / DNA-Binding Proteins: genetics / DNA-Binding
Proteins: metabolism / Dimerization / Enhancer Elements,
Genetic: genetics / Humans / Leucine Zippers: genetics /
Mice / Microphthalmia-Associated Transcription Factor:
chemistry / Microphthalmia-Associated Transcription Factor:
genetics / Microphthalmia-Associated Transcription Factor:
metabolism / Models, Molecular / Molecular Sequence Data /
Mutation / Protein Binding / Protein Structure, Tertiary /
Sequence Alignment / Waardenburg Syndrome: genetics /
DNA-Binding Proteins (NLM Chemicals) /
Microphthalmia-Associated Transcription Factor (NLM
Chemicals)},
cin = {EMBL(-2012)},
ddc = {570},
cid = {$I:(DE-H253)EMBL_-2012_-20130307$},
pnm = {DORIS Beamline BW7 (POF2-54G13)},
pid = {G:(DE-H253)POF2-BW7-20130405},
experiment = {EXP:(DE-H253)D-BW7-20150101},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:23207919},
pmc = {pmc:PMC3521630},
UT = {WOS:000311944000008},
doi = {10.1101/gad.198192.112},
url = {https://bib-pubdb1.desy.de/record/139945},
}