Structural and functional characterization of the RBBP4-ZNF827 interaction and its role in NuRD recruitment to telomeres.

Autor:	Yang SF; Telomere Length Regulation Unit, Children's Medical Research Institute, Sydney Medical School, Faculty of Medicine, University of Sydney, Westmead, NSW 2145, Australia., Sun AA; Hefei National Laboratory for Physical Sciences at Microscale and School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230027, China., Shi Y; Hefei National Laboratory for Physical Sciences at Microscale and School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230027, China., Li F; Hefei National Laboratory for Physical Sciences at Microscale and School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230027, China lifudong@ustc.edu.cn hpickett@cmri.org.au., Pickett HA; Telomere Length Regulation Unit, Children's Medical Research Institute, Sydney Medical School, Faculty of Medicine, University of Sydney, Westmead, NSW 2145, Australia lifudong@ustc.edu.cn hpickett@cmri.org.au.
Jazyk:	angličtina
Zdroj:	The Biochemical journal [Biochem J] 2018 Aug 31; Vol. 475 (16), pp. 2667-2679. Date of Electronic Publication: 2018 Aug 31.
DOI:	10.1042/BCJ20180310
Abstrakt:	The nucleosome remodeling and histone deacetylase (NuRD) complex is an essential multi-subunit protein complex that regulates higher-order chromatin structure. Cancers that use the alternative lengthening of telomere (ALT) pathway of telomere maintenance recruit NuRD to their telomeres. This interaction is mediated by the N-terminal domain of the zinc-finger protein ZNF827. NuRD-ZNF827 plays a vital role in the ALT pathway by creating a molecular platform for recombination-mediated repair. Disruption of NuRD binding results in loss of ALT cell viability. Here, we present the crystal structure of the NuRD subunit RBBP4 bound to the N-terminal 14 amino acids of ZNF827. RBBP4 forms a negatively charged channel that binds to ZNF827 through a network of electrostatic interactions. We identify the precise amino acids in RBBP4 required for this interaction and demonstrate that disruption of these residues prevents RBBP4 binding to both ZNF827 and telomeres, but is insufficient to decrease ALT activity. These data provide insights into the structural and functional determinants of NuRD activity at ALT telomeres. (© 2018 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.)
Databáze:	MEDLINE
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