https://scholar.dgist.ac.kr/handle/20.500.11750/10033 2026-04-04T13:36:39Z https://scholar.dgist.ac.kr/handle/20.500.11750/60065 Title: The disordered N-terminus modulates the conformational metamorphosis of IscU, the Fe-S cluster assembly protein Author(s): 김진해 Abstract: An iron-sulfur (Fe-S) cluster is a ubiquitous and essential cofactor for various proteins, and its imbalance can cause abnormal iron accumulation and lead to fatal diseases, such as ataxia and myopathy. The biosynthesis of Fe-S clusters depends on several critical proteins, among which IscU, the Fe-S cluster assembly protein, plays a pivotal role. IscU shows a ‘metamorphic’ structural feature; it exhibits two interconverting conformations, the structured state (S-state) and the disordered state (D-state), and both conformations have their own functionality and interaction network. However, the detailed mechanism regarding how IscU maintains its structural heterogeneity has remained enigmatic. In this study, we employed interdisciplinary approaches to elucidate that the order-disorder transition in the N-terminal region of IscU is important to modulate its metamorphic feature. We found that the degree of orderliness in the N-terminal region is positively related to the S-state stabilization, while IscU’s affinity for HscA is inversely correlated. This implies that the N-terminal disorder of IscU is maintained on purpose to optimize its physiological efficacy. We propose that this study provides unprecedented insights into the development of novel therapeutic molecules for related pathogenic processes. 2025-02-03T15:00:00Z https://scholar.dgist.ac.kr/handle/20.500.11750/46917 Title: Local disorder of transthyretin modulates its aggregation-prone propensity Author(s): Kim, Jin Hae Abstract: Transthyretin (TTR), in its native tetrameric state, is an essential transporter of thyroxine and holo-retinol binding protein for human. However, its dissociation into the mis-folded monomer facilitates abnormal aggregation of TTR, causing deposition of TTR aggregates typically in the peripheral nervous system or in the heart. Although numerous studies were conducted to elucidate the aggregation mechanism of TTR, it is still elusive which structural features are actually responsible for its aggregation. Here, we determined with nuclear magnetic resonance (NMR) spectroscopy the three-dimensional structures of the two TTR variants: amyloidogenic monomeric TTR and its less-amyloidogenic variant, T119M. Distinctive to the native tetrameric state, the misfolded monomer of TTR presented structural features in which the C-terminal beta-strand is released and the neighboring loops are perturbed. On the other hand, introduction of T119M mutation caused non-native rearrangement of the beta-strand structure; it appears that this mutation damped conformational fluctuations of the C-terminal beta-strand, which is known to be important for TTR aggregation. Finally, we also found that Hsp90 interacts with monomeric TTR more strongly than with tetrameric TTR. Taken together, our results provide the atomistic detail to explain the elevated susceptibility of monomeric TTR for aggregation, as well as the novel insight to develop therapeutic strategies for TTR amyloidosis. 2021-07-06T15:00:00Z