Structural highlights
Function
[CP190_DROME] Component of the gypsy chromatin insulator complex which is required for the function of the gypsy chromatin insulator and other endogenous chromatin insulators. Chromatin insulators are regulatory elements which establish independent domains of transcriptional activity within eukaryotic genomes. Insulators have two defining properties; they can block the communication between an enhancer and a promoter when placed between them and can also buffer transgenes from position effect variegation (PEV). Insulators are proposed to structure the chromatin fiber into independent domains of differing transcriptional potential by promoting the formation of distinct chromatin loops. This chromatin looping may involve the formation of insulator bodies, where homotypic interactions between individual subunits of the insulator complex could promote the clustering of widely spaced insulators at the nuclear periphery. Within the gypsy insulator complex, this protein may directly bind to insulator DNA at sites distinct from those recognized by su(Hw). Required during embryogenesis for axial expansion, an actin/myosin dependent process that distributes the dividing nuclei along the anterior-posterior axis of the syncytial embryo. Does not appear to play a crucial role in organizing centrosomal microtubules during mitosis.[1] [2] [3]
Publication Abstract from PubMed
CP190 is a large, multi-domain protein, first identified as a centrosome protein with oscillatory localization over the course of the cell cycle. During interphase it has a well-established role within the nucleus as a chromatin insulator. Upon nuclear envelope breakdown, there is a striking redistribution of CP190 to centrosomes and the mitotic spindle, in addition to the population at chromosomes. Here, we investigate CP190 in detail by performing domain analysis in cultured Drosophila S2 cells combined with protein structure determination by X-ray crystallography, in vitro biochemical characterization, and in vivo fixed and live imaging of cp190 mutant flies. Our analysis of CP190 identifies a novel N-terminal centrosome and microtubule (MT) targeting region, sufficient for spindle localization. This region consists of a highly conserved BTB domain and a linker region that serves as the MT binding domain. We present the 2.5 A resolution structure of the CP190 N-terminal 126 amino acids, which adopts a canonical BTB domain fold and exists as a stable dimer in solution. The ability of the linker region to robustly localize to MTs requires BTB domain-mediated dimerization. Deletion of the linker region using CRISPR significantly alters spindle morphology and leads to DNA segregation errors in the developing Drosophila brain neuroblasts. Collectively, we highlight a multivalent MT-binding architecture in CP190, which confers distinct subcellular cytoskeletal localization and function during mitosis.
Newly Characterized Region of CP190 Associates with Microtubules and Mediates Proper Spindle Morphology in Drosophila Stem Cells.,Plevock KM, Galletta BJ, Slep KC, Rusan NM PLoS One. 2015 Dec 9;10(12):e0144174. doi: 10.1371/journal.pone.0144174., eCollection 2015. PMID:26649574[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Butcher RD, Chodagam S, Basto R, Wakefield JG, Henderson DS, Raff JW, Whitfield WG. The Drosophila centrosome-associated protein CP190 is essential for viability but not for cell division. J Cell Sci. 2004 Mar 1;117(Pt 7):1191-9. PMID:14996941 doi:http://dx.doi.org/10.1242/jcs.00979
- ↑ Pai CY, Lei EP, Ghosh D, Corces VG. The centrosomal protein CP190 is a component of the gypsy chromatin insulator. Mol Cell. 2004 Dec 3;16(5):737-48. PMID:15574329 doi:http://dx.doi.org/S1097276504006732
- ↑ Chodagam S, Royou A, Whitfield W, Karess R, Raff JW. The centrosomal protein CP190 regulates myosin function during early Drosophila development. Curr Biol. 2005 Jul 26;15(14):1308-13. PMID:16051175 doi:http://dx.doi.org/S0960-9822(05)00659-7
- ↑ Plevock KM, Galletta BJ, Slep KC, Rusan NM. Newly Characterized Region of CP190 Associates with Microtubules and Mediates Proper Spindle Morphology in Drosophila Stem Cells. PLoS One. 2015 Dec 9;10(12):e0144174. doi: 10.1371/journal.pone.0144174., eCollection 2015. PMID:26649574 doi:http://dx.doi.org/10.1371/journal.pone.0144174
