Cyclin-dependent kinase 1 depolymerizes nuclear lamin filaments by disrupting the head-to-tail interaction of the lamin central rod domain.

J Biol Chem

Department of Agricultural Biotechnology, Center for Food and Bioconvergence, and Research Institute for Agriculture and Life Sciences, CALS, Seoul National University, Seoul, Republic of Korea. Electronic address:

Published: September 2022

AI Article Synopsis

  • Nuclear lamins are proteins that help maintain the structure of the nuclear envelope by forming filament structures through specific arrangements of coiled-coil dimers (A11 and A22 modes).
  • During mitosis, the phosphorylation of lamin proteins by the CDK complex leads to the breakdown of these filaments by disrupting key interactions that stabilize them, specifically the ACN interaction between different coil regions.
  • This study reveals how these changes at the molecular level influence the regulation of nuclear shape during the cell cycle, providing insights into the mechanics of nuclear morphology.

Article Abstract

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.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9400090PMC
http://dx.doi.org/10.1016/j.jbc.2022.102256DOI Listing

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