Nuclear lamins maintain the nuclear envelope structure by forming long linear filaments via two alternating molecular arrangements of coiled-coil dimers, known as A11 and A22 binding modes. The A11 binding mode is characterized by the antiparallel interactions between coil 1b domains, whereas the A22 binding mode is facilitated by interactions between the coil 2 domains of lamin. The junction between A11- and A22-interacting dimers in the lamin tetramer produces another parallel head–tail interaction between coil 1a and the C-terminal region of coil 2, called the ACN interaction. During mitosis, phosphorylation in the lamin N-terminal head region by the cyclin-dependent kinase (CDK) complex triggers depolymerization of lamin filaments, but the associated mechanisms remain unknown at the molecular level. In this study, we revealed using the purified proteins that phosphorylation by the CDK1 complex promotes disassembly of lamin filaments by directly abolishing the ACN interaction between coil 1a and the C-terminal portion of coil 2. We further observed that this interaction was disrupted as a result of alteration of the ionic interactions between coil 1a and coil 2. Combined with molecular modeling, we propose a mechanism for CDK1-dependent disassembly of the lamin filaments. Our results will help to elucidate the cell cycle–dependent regulation of nuclear morphology at the molecular level.
|Journal||Journal of Biological Chemistry|
|Publication status||Published - 2022 Sept|
Bibliographical noteFunding Information:
This work was supported by grants from the National Research Foundation of Korea (grant no.: 2019R1A2C208513512 ). This research was supported by the Basic Research Program through the National Research Foundation of Korea , funded by the Ministry of Science and ICT (grant no.: 2020R1A4A1019322 ) and the Korea Institute of Planning and Evaluation for Technology in Food, Agriculture, Forestry, and Fisheries , funded by the Ministry of Agriculture, Food, and Rural Affairs (grant no.: 321036052HD020 ).
S. J. was supported by the BK21 Plus Program of the Department of Agricultural Biotechnology, Seoul National University , Seoul, Korea.
© 2022 The Authors
All Science Journal Classification (ASJC) codes
- Molecular Biology
- Cell Biology