Publication Date:
2010-08-27
Description:
Centromeres are specified epigenetically, and the histone H3 variant CENP-A is assembled into the chromatin of all active centromeres. Divergence from H3 raises the possibility that CENP-A generates unique chromatin features to mark physically centromere location. Here we report the crystal structure of a subnucleosomal heterotetramer, human (CENP-A-H4)(2), that reveals three distinguishing properties encoded by the residues that comprise the CENP-A targeting domain (CATD; ref. 2): (1) a CENP-A-CENP-A interface that is substantially rotated relative to the H3-H3 interface; (2) a protruding loop L1 of the opposite charge as that on H3; and (3) strong hydrophobic contacts that rigidify the CENP-A-H4 interface. Residues involved in the CENP-A-CENP-A rotation are required for efficient incorporation into centromeric chromatin, indicating specificity for an unconventional nucleosome shape. DNA topological analysis indicates that CENP-A-containing nucleosomes are octameric with conventional left-handed DNA wrapping, in contrast to other recent proposals. Our results indicate that CENP-A marks centromere location by restructuring the nucleosome from within its folded histone core.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2946842/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2946842/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sekulic, Nikolina -- Bassett, Emily A -- Rogers, Danielle J -- Black, Ben E -- GM08275/GM/NIGMS NIH HHS/ -- GM82989/GM/NIGMS NIH HHS/ -- R01 GM082989/GM/NIGMS NIH HHS/ -- R01 GM082989-01A1/GM/NIGMS NIH HHS/ -- R01 GM082989-02/GM/NIGMS NIH HHS/ -- R01 GM082989-03/GM/NIGMS NIH HHS/ -- T32 GM008275/GM/NIGMS NIH HHS/ -- England -- Nature. 2010 Sep 16;467(7313):347-51. doi: 10.1038/nature09323. Epub 2010 Aug 25.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry and Biophysics, University of Pennsylvania, School of Medicine, Philadelphia, Pennsylvania 19104-6059, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20739937" target="_blank"〉PubMed〈/a〉
Keywords:
Amino Acid Sequence
;
Autoantigens/*chemistry/*metabolism
;
Binding Sites
;
Centromere/*chemistry/*metabolism
;
Chromatin Assembly and Disassembly
;
Chromosomal Proteins, Non-Histone/*chemistry/*metabolism
;
Crystallography, X-Ray
;
DNA/chemistry/metabolism
;
Deuterium Exchange Measurement
;
Epistasis, Genetic
;
Histones/*chemistry/*metabolism
;
Humans
;
Hydrogen Bonding
;
Hydrophobic and Hydrophilic Interactions
;
Models, Molecular
;
Molecular Sequence Data
;
Nucleosomes/chemistry/metabolism
;
Protein Multimerization
;
Protein Structure, Quaternary
;
Protein Structure, Tertiary
;
Rotation
;
Scattering, Small Angle
;
Structure-Activity Relationship
;
Substrate Specificity
Print ISSN:
0028-0836
Electronic ISSN:
1476-4687
Topics:
Biology
,
Chemistry and Pharmacology
,
Medicine
,
Natural Sciences in General
,
Physics
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