Mis16 Independently Recognizes Histone H4 and the CENP-ACnp1-Specific Chaperone Scm3sp
CENP-A is a centromere-specific histone H3 variant that is required for kinetochore assembly and accurate chromosome segregation. For it to function properly, CENP-A must be specifically localized to centromeres. In fission yeast, Scm3sp and the Mis18 complex, composed of Mis16, Eic1, and Mis18, function as a CENP-ACnp1-specific chaperone and a recruiting factor, respectively, and together ensure accurate delivery of CENP-ACnp1 to centromeres. Although how Scm3sp specifically recognizes CENP-ACnp1 has been revealed recently, the recruiting mechanism of CENP-ACnp1 via the Mis18 complex remains unknown. In this study, we have determined crystal structures of Schizosaccharomyces japonicus Mis16 alone and in complex with the helix 1 of histone H4 (H4α1). Crystal structures followed by mutant analysis and affinity pull-downs have revealed that Mis16 recognizes both H4α1 and Scm3sp independently within the CENP-ACnp1/H4:Scm3sp complex. This observation suggests that Mis16 gains CENP-ACnp1 specificity by recognizing both Scm3sp and histone H4. Our studies provide insights into the molecular mechanisms underlying specific recruitment of CENP-ACnp1/H4:Scm3sp into centromeres.
- Research Organization:
- Advanced Photon Source (APS), Argonne National Laboratory (ANL), Argonne, IL (US)
- Sponsoring Organization:
- OTHER
- OSTI ID:
- 1351362
- Journal Information:
- Journal of Molecular Biology, Journal Name: Journal of Molecular Biology Journal Issue: 20 Vol. 427; ISSN 0022-2836
- Publisher:
- Elsevier
- Country of Publication:
- United States
- Language:
- ENGLISH
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