| Structural highlights
2l5a is a 1 chain structure with sequence from Saccharomyces cerevisiae. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Gene: | CSE4, CSL2, YKL049C, YKL262, SCM3, YDL139C, D2155, HHF1, YBR009C, YBR0122, HHF2, YNL030W, N2752 (Saccharomyces cerevisiae) |
| Resources: | FirstGlance, OCA, RCSB, PDBsum |
Function
[CENPA_YEAST] Histone H3-like variant which exclusively replaces conventional H3 in the nucleosome core of centromeric chromatin at the inner plate of the kinetochore. Required for recruitment and assembly of kinetochore proteins, mitotic progression and chromosome segregation. May serve as an epigenetic mark that propagates centromere identity through replication and cell division. Required for functional chromatin architecture at the yeast 2-micron circle partitioning locus and promotes equal plasmid segregation.[1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [11]
Publication Abstract from PubMed
The centromere is a unique chromosomal locus that ensures accurate segregation of chromosomes during cell division by directing the assembly of a multiprotein complex, the kinetochore. The centromere is marked by a conserved variant of conventional histone H3 termed CenH3 or CENP-A (ref. 2). A conserved motif of CenH3, the CATD, defined by loop 1 and helix 2 of the histone fold, is necessary and sufficient for specifying centromere functions of CenH3 (refs 3, 4). The structural basis of this specification is of particular interest. Yeast Scm3 and human HJURP are conserved non-histone proteins that interact physically with the (CenH3-H4)(2) heterotetramer and are required for the deposition of CenH3 at centromeres in vivo. Here we have elucidated the structural basis for recognition of budding yeast (Saccharomyces cerevisiae) CenH3 (called Cse4) by Scm3. We solved the structure of the Cse4-binding domain (CBD) of Scm3 in complex with Cse4 and H4 in a single chain model. An alpha-helix and an irregular loop at the conserved amino terminus and a shorter alpha-helix at the carboxy terminus of Scm3(CBD) wraps around the Cse4-H4 dimer. Four Cse4-specific residues in the N-terminal region of helix 2 are sufficient for specific recognition by conserved and functionally important residues in the N-terminal helix of Scm3 through formation of a hydrophobic cluster. Scm3(CBD) induces major conformational changes and sterically occludes DNA-binding sites in the structure of Cse4 and H4. These findings have implications for the assembly and architecture of the centromeric nucleosome.
Structural basis for recognition of centromere histone variant CenH3 by the chaperone Scm3.,Zhou Z, Feng H, Zhou BR, Ghirlando R, Hu K, Zwolak A, Miller Jenkins LM, Xiao H, Tjandra N, Wu C, Bai Y Nature. 2011 Apr 14;472(7342):234-7. Epub 2011 Mar 16. PMID:21412236[12]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Stoler S, Keith KC, Curnick KE, Fitzgerald-Hayes M. A mutation in CSE4, an essential gene encoding a novel chromatin-associated protein in yeast, causes chromosome nondisjunction and cell cycle arrest at mitosis. Genes Dev. 1995 Mar 1;9(5):573-86. PMID:7698647
- ↑ Meluh PB, Yang P, Glowczewski L, Koshland D, Smith MM. Cse4p is a component of the core centromere of Saccharomyces cerevisiae. Cell. 1998 Sep 4;94(5):607-13. PMID:9741625
- ↑ Baker RE, Harris K, Zhang K. Mutations synthetically lethal with cep1 target S. cerevisiae kinetochore components. Genetics. 1998 May;149(1):73-85. PMID:9584087
- ↑ Keith KC, Baker RE, Chen Y, Harris K, Stoler S, Fitzgerald-Hayes M. Analysis of primary structural determinants that distinguish the centromere-specific function of histone variant Cse4p from histone H3. Mol Cell Biol. 1999 Sep;19(9):6130-9. PMID:10454560
- ↑ Keith KC, Fitzgerald-Hayes M. CSE4 genetically interacts with the Saccharomyces cerevisiae centromere DNA elements CDE I and CDE II but not CDE III. Implications for the path of the centromere dna around a cse4p variant nucleosome. Genetics. 2000 Nov;156(3):973-81. PMID:11063678
- ↑ Glowczewski L, Yang P, Kalashnikova T, Santisteban MS, Smith MM. Histone-histone interactions and centromere function. Mol Cell Biol. 2000 Aug;20(15):5700-11. PMID:10891506
- ↑ Tanaka T, Cosma MP, Wirth K, Nasmyth K. Identification of cohesin association sites at centromeres and along chromosome arms. Cell. 1999 Sep 17;98(6):847-58. PMID:10499801
- ↑ Biggins S, Bhalla N, Chang A, Smith DL, Murray AW. Genes involved in sister chromatid separation and segregation in the budding yeast Saccharomyces cerevisiae. Genetics. 2001 Oct;159(2):453-70. PMID:11606525
- ↑ Morey L, Barnes K, Chen Y, Fitzgerald-Hayes M, Baker RE. The histone fold domain of Cse4 is sufficient for CEN targeting and propagation of active centromeres in budding yeast. Eukaryot Cell. 2004 Dec;3(6):1533-43. PMID:15590827 doi:http://dx.doi.org/10.1128/EC.3.6.1533-1543.2004
- ↑ Collins KA, Castillo AR, Tatsutani SY, Biggins S. De novo kinetochore assembly requires the centromeric histone H3 variant. Mol Biol Cell. 2005 Dec;16(12):5649-60. Epub 2005 Oct 5. PMID:16207811 doi:http://dx.doi.org/10.1091/mbc.E05-08-0771
- ↑ Hajra S, Ghosh SK, Jayaram M. The centromere-specific histone variant Cse4p (CENP-A) is essential for functional chromatin architecture at the yeast 2-microm circle partitioning locus and promotes equal plasmid segregation. J Cell Biol. 2006 Sep 11;174(6):779-90. PMID:16966420 doi:http://dx.doi.org/jcb.200603042
- ↑ Zhou Z, Feng H, Zhou BR, Ghirlando R, Hu K, Zwolak A, Miller Jenkins LM, Xiao H, Tjandra N, Wu C, Bai Y. Structural basis for recognition of centromere histone variant CenH3 by the chaperone Scm3. Nature. 2011 Apr 14;472(7342):234-7. Epub 2011 Mar 16. PMID:21412236 doi:10.1038/nature09854
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