Acquisition of Myogenic Specificity through Replacement of One Amino Acid of MASH-1 and Introduction of an Additional alpha -Helical Turn
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C. Dezan
Abstract
The homologous transcription factors Myf-5, MyoD, myogenin, MRF-4, and MASH-1 bind with high affinity and modest sequence specificity to DNA containing an E-box (CANNTG). This similarity of the in vitro DNA binding specificity is in sharp contrast to the high physiological specificity displayed by these proteins. Myf-5, MyoD, myogenin, and MRF-4 induce cells to differentiate along a myogenic pathway, while MASH-1 promotes the differentiation of neuronal precursor cells. We show here that MASH-1 can be converted into a protein capable of inducing myogenesis in fibroblasts by replacing leucine (130) of MASH-1 with lysine and introducing an additional turn into its basic recognition helix. These changes do not significantly alter the DNA binding properties of the proteins in cell free conditions. Crystallographic data for the DNA complexes of MyoD and E12 suggest that Leu (130) points away from the DNA into the solvent. We postulate that the identity of the amino acid in position 130 is important for protein-protein interactions that might affect the DNA binding specificities displayed by BHLH-proteins in vivo and form the molecular basis of the different physiological properties of the myogenic and neurogenic BHLH-proteins.
Copyright © 1999 by Walter de Gruyter GmbH & Co. KG
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Articles in the same Issue
- To Our Authors, Readers and Subscribers
- Michael Strauss. January 12, 1950 April 29, 1999
- Monoallelic Expression of Pax5: A Paradigm for the Haploinsufficiency of Mammalian Pax Genes?
- Adeno-Associated Viral Vectors for Gene Transfer and Gene Therapy
- Histidyl-tRNA Synthetase
- Dequalinium TM Vesicles Form Stable Complexes with Plasmid DNA which Are Protected from DNase Attack
- On the Role of Thymopoietins in Cell Proliferation. Immunochemical Evidence for New Members of the Human Thymopoietin Family
- Functional Characterization of Atherosclerosis-Associated Ser128Arg and Leu554Phe E-Selectin Mutations
- Cycloheximide, a New Tool to Dissect Specific Steps in ER-Associated Degradation of Different Substrates
- Localization of Rat Cathepsin K in Osteoclasts and Resorption Pits: Inhibition of Bone Resorption and Cathepsin K-Activity by Peptidyl Vinyl Sulfones
- Oxidation of 4-tert-Butylcatechol and Dopamine by Hydrogen Peroxide Catalysed by Horseradisch Peroxidase
- A Non-Radioactive Method for Inexpensive Quantitative RT-PCR
- Activation of the Transcription Factor ISGF3 by Interferon-gamma
- Acquisition of Myogenic Specificity through Replacement of One Amino Acid of MASH-1 and Introduction of an Additional alpha -Helical Turn
- The Heavy Metal-Responsive Transcription Factor-1 (MTF-1) Is Not Required for Neural Differentiation
- Human Fc gamma Receptor IIb Expressed in <I>Escherichia coli</I> Reveals IgG Binding Capability
- Mutational Analysis of Two Stefin A Epitopes
