6XWT

drosophila melanogaster CENP-A/H4 bound to N-terminal CAL1 fragment

Summary for 6XWT

• Entry DOI: 10.2210/pdb6xwt/pdb
• Descriptor: Histone H3-like centromeric protein cid, Histone H4, Chromosome alignment defect 1 (3 entities in total)
• Functional Keywords: centromere, kinetochore, cell division, cell cycle
• Biological source: Drosophila melanogaster (Fruit fly); More
• Total number of polymer chains: 6
• Total formula weight: 294280.88

Authors

Jeyaprakash, A.A.,Medina-Pritchard, B.,Lazou, V.,Zou, J.,Byron, O.,Abad, M.A.,Rappsilber, J.,Heun, P. (deposition date: 2020-01-24, release date: 2020-04-01, Last modification date: 2024-01-24)

Primary citation

Medina-Pritchard, B.,Lazou, V.,Zou, J.,Byron, O.,Abad, M.A.,Rappsilber, J.,Heun, P.,Jeyaprakash, A.A.
Structural basis for centromere maintenance by Drosophila CENP-A chaperone CAL1.
Embo J., 39:e103234-e103234, 2020

PubMed Abstract: Centromeres are microtubule attachment sites on chromosomes defined by the enrichment of histone variant CENP-A-containing nucleosomes. To preserve centromere identity, CENP-A must be escorted to centromeres by a CENP-A-specific chaperone for deposition. Despite this essential requirement, many eukaryotes differ in the composition of players involved in centromere maintenance, highlighting the plasticity of this process. In humans, CENP-A recognition and centromere targeting are achieved by HJURP and the Mis18 complex, respectively. Using X-ray crystallography, we here show how Drosophila CAL1, an evolutionarily distinct CENP-A histone chaperone, binds both CENP-A and the centromere receptor CENP-C without the requirement for the Mis18 complex. While an N-terminal CAL1 fragment wraps around CENP-A/H4 through multiple physical contacts, a C-terminal CAL1 fragment directly binds a CENP-C cupin domain dimer. Although divergent at the primary structure level, CAL1 thus binds CENP-A/H4 using evolutionarily conserved and adaptive structural principles. The CAL1 binding site on CENP-C is strategically positioned near the cupin dimerisation interface, restricting binding to just one CAL1 molecule per CENP-C dimer. Overall, by demonstrating how CAL1 binds CENP-A/H4 and CENP-C, we provide key insights into the minimalistic principles underlying centromere maintenance.

PubMed: 32134144
DOI: 10.15252/embj.2019103234

Experimental method

X-RAY DIFFRACTION (3.47 Å)