Investigation of the functional mechanism of small G protein Ran - Czigléczki Janka PhD-védése, 2026.05.27. 14:00

2026. május 22

Hír bevezető kép
 
Szeretettel várunk minden érdeklődőt Czigléczki Janka munkatársunk doktori védésére.
 
Időpont: 2026.05.27. 14:00
Helyszín: SE Elméleti Orvostudományi Központ, Hevesy György előadóterem, 1094 Budapest, Tűzoltó utca 37-47.
 
Title: Investigation of the functional mechanism of small G protein Ran
Supervisor: Erika Balog PhD, Dr. habil.
 
Summary: Molecular dynamics (MD) simulations are a valuable method for exploring the conformational changes of small GTPases. We examined how the conformational dynamics of Ran depend on the bound nucleotide, focusing specifically on the C-terminal region and the molecular mechanism of switch I opening, using MD and aMDeNM simulations. Our results reveal pronounced nucleotide-dependent differences in Ran dynamics. In the GTP-bound state, the C-terminus exhibits substantially higher flexibility than in the GDP-bound form. These features suggest that Ran requires greater conformational flexibility in its active form, consistent with its role in nucleocytoplasmic transport.
Across all simulations, a conserved anchoring interaction between the N-terminal segment of the C-terminus and the α5-β2 interface of the G-domain was identified, providing a structural explanation for the frequent disorder of distal C-terminal residues in RanGTP crystal structures.
In addition, our study elucidates the molecular basis of switch I opening in RanGTP. Disruption of Mg²⁺ coordination alone induces only a partially open switch I conformation corresponding to the state 1 conformation described for Ras proteins, an open, effector-nonbinding state. A full transition to the RanGDP-like, fully open switch I conformation requires coordinated disruption of both Mg²⁺ coordination and the Phe35-GTP-Lys152 stabilizing triad. Triad destabilization is initiated by reorientation of Lys152 toward Glu186, leading to formation of a Lys152-Glu186 salt bridge. Together, these findings define a two-step mechanism for switch I opening and provide a framework for understanding Ran’s unique conformational regulation.