PhD Scientific Days 2025

Poster Session III. - H: Pharmaceutical Sciences and Health Technologies

Characterization of the Allosteric Effects in the CRM1-RanGTP Complex Formation

Name of the presenter

Czigléczki Janka

Institute/workplace of the presenter

Department of Biophysics and Radiation Biology, Semmelweis University, Budapest, Hungary

Authors

Janka Czigléczki¹, Hyunbum Jang², Ruth Nussinov², Erika Balog¹

1: Department of Biophysics and Radiation Biology, Semmelweis University, Budapest, Hungary
2: Computational Structural Biology Section, Frederick National Laboratory for Cancer Research in the Cancer Innovation Laboratory, National Cancer Institute, Frederick, MD, United States

Text of the abstract

Small GTPase Ran (Ras-related Nuclear protein) is the main regulator of the nucleo-cytoplasmic transport through the nuclear pore complex. It functions as a molecular switch cycling between the GDP-bound inactive, “off” state, and the GTP-bound active, “on” state. Since deregulation of Ran is linked to numerous cancers, understanding the complexity of its regulatory mechanism is critical for drug discovery. One of the partners in the nucleo-cytoplasmic transport is the export receptor CRM1 (chromosome region maintenance 1). CRM1 cooperatively binds RanGTP and cargo in the nucleus. In the transport complex, RanGTP is localized within the ring-like structure of CRM1. In the crystal structures of the CRM1-RanGTP, the structure of the Ran C-terminal segment remains unresolved. Using MD simulations, our goal was to uncover the molecular mechanisms that start from the CRM1-RanGTP binding and lead to the closed macromolecular complex.

This project was partially funded by the TKP2021-EGA-23 provided by the Ministry of Innovation and Technology of Hungary; by federal funds from the National Cancer Institute, National Institutes of Health, under contract HHSN261201500003I, and by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research.