4rkg

From Proteopedia

Structure of the MSL2 CXC domain bound with a non-specific (GC)6 DNA

PDB ID 4rkg

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Structural highlights

4rkg is a 4 chain structure with sequence from Drosophila melanogaster. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

MSL2_DROME The Msl proteins are essential for elevating transcription of the single X chromosome in the male (X chromosome dosage compensation). Msl-2 is required for translation and/or stability of msl-1 in males. In complex with msl-1, acts as an E3 ubiquitin ligase that promotes ubiquitination of histone H2B.^[1] ^[2] ^[3] ^[4]

Publication Abstract from PubMed

The male-specific lethal dosage compensation complex (MSL-DCC) selectively assembles on the X chromosome in Drosophila males and activates gene transcription by twofold through histone acetylation. An MSL recognition element (MRE) sequence motif nucleates the initial MSL association, but how it is recognized remains unknown. Here, we identified the CXC domain of MSL2 specifically recognizing the MRE motif and determined its crystal structure bound to specific and nonspecific DNAs. The CXC domain primarily contacts one strand of DNA duplex and employs a single arginine to directly read out dinucleotide sequences from the minor groove. The arginine is flexible when bound to nonspecific sequences. The core region of the MRE motif harbors two binding sites on opposite strands that can cooperatively recruit a CXC dimer. Specific DNA-binding mutants of MSL2 are impaired in MRE binding and X chromosome localization in vivo. Our results reveal multiple dynamic DNA-binding modes of the CXC domain that target the MSL-DCC to X chromosomes.

Structural basis of X chromosome DNA recognition by the MSL2 CXC domain during Drosophila dosage compensation.,Zheng S, Villa R, Wang J, Feng Y, Wang J, Becker PB, Ye K Genes Dev. 2014 Dec 1;28(23):2652-62. doi: 10.1101/gad.250936.114. PMID:25452275^[5]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Wu L, Zee BM, Wang Y, Garcia BA, Dou Y. The RING finger protein MSL2 in the MOF complex is an E3 ubiquitin ligase for H2B K34 and is involved in crosstalk with H3 K4 and K79 methylation. Mol Cell. 2011 Jul 8;43(1):132-44. doi: 10.1016/j.molcel.2011.05.015. PMID:21726816 doi:http://dx.doi.org/10.1016/j.molcel.2011.05.015
↑ Bashaw GJ, Baker BS. The msl-2 dosage compensation gene of Drosophila encodes a putative DNA-binding protein whose expression is sex specifically regulated by Sex-lethal. Development. 1995 Oct;121(10):3245-58. PMID:7588059
↑ Kelley RL, Solovyeva I, Lyman LM, Richman R, Solovyev V, Kuroda MI. Expression of msl-2 causes assembly of dosage compensation regulators on the X chromosomes and female lethality in Drosophila. Cell. 1995 Jun 16;81(6):867-77. PMID:7781064
↑ Zhou S, Yang Y, Scott MJ, Pannuti A, Fehr KC, Eisen A, Koonin EV, Fouts DL, Wrightsman R, Manning JE, et al.. Male-specific lethal 2, a dosage compensation gene of Drosophila, undergoes sex-specific regulation and encodes a protein with a RING finger and a metallothionein-like cysteine cluster. EMBO J. 1995 Jun 15;14(12):2884-95. PMID:7796814
↑ Zheng S, Villa R, Wang J, Feng Y, Wang J, Becker PB, Ye K. Structural basis of X chromosome DNA recognition by the MSL2 CXC domain during Drosophila dosage compensation. Genes Dev. 2014 Dec 1;28(23):2652-62. doi: 10.1101/gad.250936.114. PMID:25452275 doi:http://dx.doi.org/10.1101/gad.250936.114