Home > Publications database > Restricted leucine zipper dimerization and specificity of DNA recognition of the melanocyte master regulator MITF > print

001     139945
005     20250730162609.0
024 7 _ |a pmid:23207919
|2 pmid
024 7 _ |a pmc:PMC3521630
|2 pmc
024 7 _ |a 1549-5477
|2 ISSN
024 7 _ |a 0890-9369
|2 ISSN
024 7 _ |a 10.1101/gad.198192.112
|2 doi
024 7 _ |a WOS:000311944000008
|2 WOS
024 7 _ |a altmetric:1117956
|2 altmetric
024 7 _ |a openalex:W2127845119
|2 openalex
037 _ _ |a PHPPUBDB-24647
041 _ _ |a eng
082 _ _ |a 570
100 1 _ |a Pogenberg, V.
|0 P:(DE-H253)PIP1013622
|b 0
110 1 _ |a DESY
|b European Molecular Biology Laboratory
245 _ _ |a Restricted leucine zipper dimerization and specificity of DNA recognition of the melanocyte master regulator MITF
260 _ _ |a Stanford, Calif.
|c 2012
|b HighWire Press
300 _ _ |a 2647-2658
336 7 _ |a Journal Article
|0 0
|2 EndNote
336 7 _ |a article
|2 DRIVER
336 7 _ |a Journal Article
|b journal
|m journal
|0 PUB:(DE-HGF)16
|2 PUB:(DE-HGF)
336 7 _ |a ARTICLE
|2 BibTeX
440 _ 0 |a Genes Develop.
|0 PERI:(DE-600)1467414-2
|v 26
|y 23
|x 0890-9369
500 _ _ |a (c) Cold Spring Harbor Laboratory Press
520 _ _ |a 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.
536 _ _ |0 G:(DE-H253)POF2-BW7-20130405
|f POF II
|x 0
|c POF2-54G13
|a DORIS Beamline BW7 (POF2-54G13)
588 _ _ |a Dataset connected to Pubmed
650 _ 7 |a DNA-Binding Proteins
|0 0
|2 NLM Chemicals
650 _ 7 |a Microphthalmia-Associated Transcription Factor
|0 0
|2 NLM Chemicals
650 _ 2 |a Amino Acid Sequence
|2 MeSH
650 _ 2 |a Animals
|2 MeSH
650 _ 2 |a DNA-Binding Proteins: chemistry
|2 MeSH
650 _ 2 |a DNA-Binding Proteins: genetics
|2 MeSH
650 _ 2 |a DNA-Binding Proteins: metabolism
|2 MeSH
650 _ 2 |a Dimerization
|2 MeSH
650 _ 2 |a Enhancer Elements, Genetic: genetics
|2 MeSH
650 _ 2 |a Humans
|2 MeSH
650 _ 2 |a Leucine Zippers: genetics
|2 MeSH
650 _ 2 |a Mice
|2 MeSH
650 _ 2 |a Microphthalmia-Associated Transcription Factor: chemistry
|2 MeSH
650 _ 2 |a Microphthalmia-Associated Transcription Factor: genetics
|2 MeSH
650 _ 2 |a Microphthalmia-Associated Transcription Factor: metabolism
|2 MeSH
650 _ 2 |a Models, Molecular
|2 MeSH
650 _ 2 |a Molecular Sequence Data
|2 MeSH
650 _ 2 |a Mutation
|2 MeSH
650 _ 2 |a Protein Binding
|2 MeSH
650 _ 2 |a Protein Structure, Tertiary
|2 MeSH
650 _ 2 |a Sequence Alignment
|2 MeSH
650 _ 2 |a Waardenburg Syndrome: genetics
|2 MeSH
693 _ _ |a DORIS III
|f DORIS Beamline BW7
|1 EXP:(DE-H253)DORISIII-20150101
|0 EXP:(DE-H253)D-BW7-20150101
|6 EXP:(DE-H253)D-BW7-20150101
|x 0
700 1 _ |a Oegmundsdottir, M. H.
|0 P:(DE-HGF)0
|b 1
700 1 _ |a Bergsteinsdottir, K.
|0 P:(DE-HGF)0
|b 2
700 1 _ |a Schepsky, A.
|0 P:(DE-HGF)0
|b 3
700 1 _ |a Phung, B.
|0 P:(DE-HGF)0
|b 4
700 1 _ |a Deineko, V.
|0 P:(DE-H253)PIP1013805
|b 5
700 1 _ |a Milewski, M.
|0 P:(DE-H253)PIP1014518
|b 6
700 1 _ |a Steingrimsson, E.
|0 P:(DE-HGF)0
|b 7
700 1 _ |a Wilmanns, M.
|0 P:(DE-H253)PIP1001283
|b 8
773 _ _ |a 10.1101/gad.198192.112
|g Vol. 26, p. 2647-2658
|0 PERI:(DE-600)1467414-2
|q 26<2647-2658
|p 2647-2658
|t Genes & development
|v 26
|y 2012
|x 0890-9369
856 4 0 |u http://genesdev.cshlp.org/content/26/23/2647.long
856 7 _ |2 Pubmed Central
|u http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3521630
856 4 _ |u https://bib-pubdb1.desy.de/record/139945/files/Restricted.pdf
|y OpenAccess
856 4 _ |u https://bib-pubdb1.desy.de/record/139945/files/Restricted.jpg?subformat=icon-1440
|x icon-1440
|y OpenAccess
856 4 _ |u https://bib-pubdb1.desy.de/record/139945/files/Restricted.jpg?subformat=icon-180
|x icon-180
|y OpenAccess
856 4 _ |u https://bib-pubdb1.desy.de/record/139945/files/Restricted.jpg?subformat=icon-640
|x icon-640
|y OpenAccess
909 _ _ |o oai:hh0024.library.desy.de:24647
909 C O |o oai:bib-pubdb1.desy.de:139945
|p openaire
|p open_access
|p VDB
|p driver
|p dnbdelivery
910 1 _ |0 I:(DE-HGF)0
|a Externes Institut
|k Extern
913 1 _ |b Struktur der Materie
|1 G:(DE-HGF)POF2-540
|0 G:(DE-HGF)POF2-54G13
|2 G:(DE-HGF)POF2-500
|v DORIS III
|9 G:(DE-H253)POF2-BW7-20130405
|x 0
|a DE-H253
|4 G:(DE-HGF)POF
|3 G:(DE-HGF)POF2
|l Forschung mit Photonen, Neutronen, Ionen
914 1 _ |y 2012
915 _ _ |a Medline
|0 StatID:(DE-HGF)0300
|2 StatID
915 _ _ |a OpenAccess
|0 StatID:(DE-HGF)0510
|2 StatID
915 _ _ |a No Author Disambiguation
|0 StatID:(DE-HGF)1
|2 StatID
920 1 _ |0 I:(DE-H253)EMBL_-2012_-20130307
|k EMBL(-2012)
|l EMBL
|x 0
920 _ 1 |i European Molecular Biology Laboratory
|k EMBL
920 _ _ |k 001
980 _ _ |a journal
980 _ _ |a VDB
980 _ _ |a PHPPUBDB
980 _ _ |a UNRESTRICTED
980 _ _ |a ConvertedRecord
980 _ _ |a FullTexts
980 _ _ |a I:(DE-H253)EMBL_-2012_-20130307
980 1 _ |a FullTexts

LibraryCollectionCLSMajorCLSMinorLanguageAuthor
Marc 21