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RCC1 uses a conformationally diverse loop region to interact with the nucleosome: a model for the RCC1-nucleosome complex. | LitMetric

RCC1 uses a conformationally diverse loop region to interact with the nucleosome: a model for the RCC1-nucleosome complex.

J Mol Biol

Center for Eukaryotic Gene Regulation, Department of Biochemistry and Molecular Biology, 108 Althouse Laboratory, The Pennsylvania State University, University Park, PA 16802-1014, USA.

Published: May 2010

AI Article Synopsis

  • RCC1 is crucial for key cellular functions like mitosis and nuclear envelope formation, as it recruits the protein Ran to chromatin and establishes a gradient essential for these processes.
  • New research indicates that RCC1 binds to nucleosomes (the building blocks of chromatin) not via the previously thought method but using a flexible region called the switchback loop along with its N-terminal tail.
  • This novel binding mechanism clarifies how RCC1 interacts with Ran and explains the dynamics of Ran's binding to nucleosomes, enhancing our understanding of RCC1's role in cellular functions.

Article Abstract

The binding of RCC1 (regulator of chromosome condensation 1) to chromatin is critical for cellular processes such as mitosis, nucleocytoplasmic transport, and nuclear envelope formation because RCC1 recruits the small GTPase Ran (Ras-related nuclear protein) to chromatin and sets up a Ran-GTP gradient around the chromosomes. However, the molecular mechanism by which RCC1 binds to nucleosomes, the repeating unit of chromatin, is not known. We have used biochemical approaches to test structural models for how the RCC1 beta-propeller protein could bind to the nucleosome. In contrast to the prevailing model, RCC1 does not appear to use the beta-propeller face opposite to its Ran-binding face to interact with nucleosomes. Instead, we find that RCC1 uses a conformationally flexible loop region we have termed the switchback loop in addition to its N-terminal tail to bind to the nucleosome. The juxtaposition of the RCC1 switchback loop to its Ran binding surface suggests a novel mechanism for how nucleosome-bound RCC1 recruits Ran to chromatin. Furthermore, this model accounts for previously unexplained observations for how Ran can interact with the nucleosome both dependent and independent of RCC1 and how binding of the nucleosome can enhance RCC1's Ran nucleotide exchange activity.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2895563PMC
http://dx.doi.org/10.1016/j.jmb.2010.03.037DOI Listing

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