期刊
STRUCTURE
卷 29, 期 9, 页码 975-+出版社
CELL PRESS
DOI: 10.1016/j.str.2021.04.011
关键词
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资金
- CIHR foundation grant [FDN-143277]
- NSERC PGS D
- National Institute of General Medical Sciences from the National Institutesof Health [P30 GM124165]
- DOE Office of Science [DE-AC02-06CH11357]
Skp2 and cyclin A are cell-cycle regulators that control the activity of CDK2; the N terminus of Skp2 can interact directly with cyclin A. The structure of the complex between the N terminus of Skp2 and cyclin A reveals a bipartite mode of interaction with two motifs in Skp2 recognizing two discrete surfaces on cyclin A, shedding light on the inhibitory effect of Skp2 on CDK2-cyclin A kinase activity.
Skp2 and cyclin A are cell-cycle regulators that control the activity of CDK2. Cyclin A acts as an activator and substrate recruitment factor of CDK2, while Skp2 mediates the ubiquitination and subsequent destruction of the CDK inhibitor protein p27. The N terminus of Skp2 can interact directly with cyclin A but is not required for p27 ubiquitination. To gain insight into this poorly understood interaction, we have solved the 3.2 angstrom X-ray crystal structure of the N terminus of Skp2 bound to cyclin A. The structure reveals a bipartite mode of interaction with two motifs in Skp2 recognizing two discrete surfaces on cyclin A. The uncovered binding mechanism allows for a rationalization of the inhibitory effect of Skp2 on CDK2-cyclin A kinase activity toward the RxL motif containing substrates and raises the possibility that other intermolecular regulators and substrates may use similar non-canonical modes of interaction for cyclin targeting.
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