3NQU

Crystal structure of partially trypsinized (CENP-A/H4)2 heterotetramer

Summary for 3NQU

• Entry DOI: 10.2210/pdb3nqu/pdb
• Related: 3NQJ
• Descriptor: Histone H3-like centromeric protein A, Histone H4, SULFATE ION, ... (4 entities in total)
• Functional Keywords: alpha helix, histone fold, centromere, dna binding protein
• Biological source: Homo sapiens (human); More
• Cellular location: Nucleus: P49450 P62805
• Total number of polymer chains: 2
• Total formula weight: 27898.37

Authors

Sekulic, N.,Black, B.E. (deposition date: 2010-06-29, release date: 2010-08-25, Last modification date: 2023-09-06)

Primary citation

Sekulic, N.,Bassett, E.A.,Rogers, D.J.,Black, B.E.
The structure of (CENP-A-H4)(2) reveals physical features that mark centromeres.
Nature, 467:347-351, 2010

PubMed Abstract: 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.

PubMed: 20739937
DOI: 10.1038/nature09323

Experimental method

X-RAY DIFFRACTION (2.5 Å)