5h5p
From Proteopedia
Crystal structure of Myelin-gene Regulatory Factor DNA binding domain
Structural highlights
FunctionMYRF_MOUSE Myelin regulatory factor: Constitutes a precursor of the transcription factor. Mediates the autocatalytic cleavage that releases the Myelin regulatory factor, N-terminal component that specifically activates transcription of central nervous system (CNS) myelin genes.[1] Myelin regulatory factor, C-terminal: Membrane-bound part that has no transcription factor activity and remains attached to the endoplasmic reticulum membrane following cleavage.[2] Myelin regulatory factor, N-terminal: Transcription factor that specifically activates expression of myelin genes such as MBP, MOG, MAG, DUSP15 and PLP1 during oligodendrocyte (OL) maturation, thereby playing a central role in oligodendrocyte maturation and CNS myelination (PubMed:19596243, PubMed:22956843, PubMed:23966833, PubMed:24204311, PubMed:27532821). Specifically recognizes and binds DNA sequence 5'-CTGGYAC-3' in the regulatory regions of myelin-specific genes and directly activates their expression. Not only required during oligodendrocyte differentiation but is also required on an ongoing basis for the maintenance of expression of myelin genes and for the maintenance of a mature, viable oligodendrocyte phenotype (PubMed:19596243, PubMed:22956843, PubMed:23966833).[3] [4] [5] [6] [7] Publication Abstract from PubMedMyelin-gene Regulatory Factor (MyRF) is one of the master transcription factors controlling myelin formation and development in oligodendrocytes which is crucial for the powerful brain functions. The N-terminal of MyRF, which contains a proline-rich region and a DNA binding domain (DBD), is auto-cleaved from the ER membrane, and then enters the nucleus to participate in transcription regulation of the myelin genes. Here we report the crystal structure of MyRF DBD. It shows an Ig-fold like architecture which consists of two antiparallel beta-sheets with 7 main strands, packing against each other, forming a beta-sandwich. Compared to its homolog, Ndt80, MyRF has a smaller and less complex DBD lacking the helices and the big loops outside the core. Structural alignment reveals that MyRF DBD possess less interaction sites with DNA than Ndt80 and may bind only at the major groove of DNA. Moreover, the structure reveals a trimeric assembly, agreeing with the previous report that MyRF DBD functions as a trimer. The mutant that we designed based on the structure disturbed trimer formation, but didn't affect the auto-cleavage reaction. It demonstrates that the activation of self-cleavage reaction of MyRF is independent of the presence of its N-terminal DBD homotrimer. The structure reported here will help to understand the molecular mechanism underlying the important roles of MyRF in myelin formation and development. Crystal structure of the DNA-binding domain of Myelin-gene Regulatory Factor.,Zhen X, Li B, Hu F, Yan S, Meloni G, Li H, Shi N Sci Rep. 2017 Jun 16;7(1):3696. doi: 10.1038/s41598-017-03768-9. PMID:28623291[8] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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Categories: Large Structures | Mus musculus | Li B | Shi N | Zhen X
