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bioRxiv · 10.1101/2022.06.24.497480

The cryo-EM structure of the CENP-A nucleosome in complex with ggKNL2

Jiang, H.·Ariyoshi, M.·Watanabe, R.·Makino, F.·Namba, K.·Fukagawa, T.
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Abstract

Centromere protein A (CENP-A) nucleosome is an epigenetic marker that specifies centromere position. The Mis18 complex is a licensing factor for new CENP-A deposition via the CENP-A chaperone, Holliday junction recognition protein (HJURP) on the centromere chromatin. Chicken KINETOCHORE NULL2 (KNL2) (ggKNL2), a Mis18 complex component, has a CENP-C-like motif, and our previous study suggested that ggKNL2 directly binds to the CENP-A nucleosome to recruit HJURP/CENP-A to the centromere. However, the molecular basis for CENP-A nucleosome recognition by ggKNK2 remains unclear. Here, we present the cryo-EM structure of the chicken CENP-A nucleosome in complex with a ggKNL2 fragment containing a CENP-C-like motif. Chicken KNL2 distinguishes between CENP-A and histone H3 in the nucleosome using the CENP-C-like motif and its downstream region. Both the C-terminal tail and RG-loop of CENP-A are simultaneously recognized as CENP-A characteristics. The CENP-A nucleosome-ggKNL2 interaction is thus essential for CENP-A deposition. Furthermore, our structural, biochemical, and cell biology data indicate that ggKNL2 alters its binding partner at the centromere during chicken cell cycle progression.

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Jiang, H., Ariyoshi, M., Watanabe, R., Makino, F., Namba, K., Fukagawa, T.. 2022-06-24. The cryo-EM structure of the CENP-A nucleosome in complex with ggKNL2. https://doi.org/10.1101/2022.06.24.497480

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