High-resolution cryo-EM of a small protein complex: The structure of the human CDK-activating kinase.
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Embargo End Date
ICR Authors
Authors
Greber, BJ
Document Type
Journal Article
Date
2024-03-25
Date Accepted
2024-03-07
Abstract
The human CDK-activating kinase (CAK) is a multifunctional protein complex and key regulator of cell growth and division. Because of its critical functions in regulating the cell cycle and transcription initiation, it is a key target for multiple cancer drug discovery programs. However, the structure of the active human CAK, insights into its regulation, and its interactions with cellular substrates and inhibitors remained elusive until recently due to the lack of high-resolution structures of the intact complex. This review covers the progress in structure determination of the human CAK by cryogenic electron microscopy (cryo-EM), from early efforts to recent near-atomic resolution maps routinely resolved at 2Å or better. These results were enabled by the latest cryo-EM technologies introduced after the initial phase of the "resolution revolution" and allowed the application of high-resolution methods to new classes of molecular targets, including small protein complexes that were intractable using earlier technology.
Citation
Structure, 2024, 32 (4), pp. S0969-2126(24)00085-6 -
Source Title
Structure
Publisher
CELL PRESS
ISSN
0969-2126
eISSN
1878-4186
1878-4186
1878-4186
Collections
Research Team
Struct Biol DNA repair