• 한국자기공명학회논문지
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• 제27권3호
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• pp.17-22
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• 2023

Bloom syndrome protein (BLM) is a pivotal RecQ helicase necessary for genetic stability through DNA repair processes. Our investigation focuses on the N-terminal region of BLM, which has been considered as an intrinsically disordered region (IDR). This IDR plays a critical role in DNA metabolism by interacting with other proteins. In this study, we performed triple resonance experiments of BLM_220-300 and presented the backbone chemical shifts. The secondary structure prediction based on chemical shifts of the backbone atoms shows the region is disordered. Our data could help further interaction studies between BLM_220-300 and its binding partners using NMR.

• Molecules and Cells
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• 제41권10호
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• pp.889-899
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• 2018

Intrinsically disordered proteins (IDPs) are highly unorthodox proteins that do not form three-dimensional structures under physiological conditions. The discovery of IDPs has destroyed the classical structure-function paradigm in protein science, 3-D structure = function, because IDPs even without well-folded 3-D structures are still capable of performing important biological functions and furthermore are associated with fatal diseases such as cancers, neurodegenerative diseases and viral pandemics. Pre-structured motifs (PreSMos) refer to transient local secondary structural elements present in the target-unbound state of IDPs. During the last two decades PreSMos have been steadily acknowledged as the critical determinants for target binding in dozens of IDPs. To date, the PreSMo concept provides the most convincing structural rationale explaining the IDP-target binding behavior at an atomic resolution. Here we present a brief developmental history of PreSMos and describe their common characteristics. We also provide a list of newly discovered PreSMos along with their functional relevance.

• Molecules and Cells
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• 제45권7호
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• pp.444-453
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• 2022

Multivalent macromolecular interactions underlie dynamic regulation of diverse biological processes in ever-changing cellular states. These interactions often involve binding of multiple proteins to a linear lattice including intrinsically disordered proteins and the chromosomal DNA with many repeating recognition motifs. Quantitative understanding of such multivalent interactions on a linear lattice is crucial for exploring their unique regulatory potentials in the cellular processes. In this review, the distinctive molecular features of the linear lattice system are first discussed with a particular focus on the overlapping nature of potential protein binding sites within a lattice. Then, we introduce two general quantitative frameworks, combinatorial and conditional probability models, dealing with the overlap problem and relating the binding parameters to the experimentally measurable properties of the linear lattice-protein interactions. To this end, we present two specific examples where the quantitative models have been applied and further extended to provide biological insights into specific cellular processes. In the first case, the conditional probability model was extended to highlight the significant impact of nonspecific binding of transcription factors to the chromosomal DNA on gene-specific transcriptional activities. The second case presents the recently developed combinatorial models to unravel the complex organization of target protein binding sites within an intrinsically disordered region (IDR) of a nucleoporin. In particular, these models have suggested a unique function of IDRs as a molecular switch coupling distinct cellular processes. The quantitative models reviewed here are envisioned to further advance for dissection and functional studies of more complex systems including phase-separated biomolecular condensates.

• 한국자기공명학회논문지
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• 제18권1호
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• pp.30-35
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• 2014

The transcription factor CP2 regulates various biological systems at diverse tissues and cells. However, none of the four CP2 isoforms has been solved in structure yet. In particular, two different regions of the CP2b isoform have been characterized to interact with the PIAS1 in nucleus to regulate the ${\alpha}$-globin gene expression. Among them, in this study, the region encompassing residues 251-309 of CP2b was prepared as a recombinant protein and its solution structure was characterized by NMR spectroscopy. The results indicated that the CP2b(251-309) fold belongs to typical IDRs (intrinsically disordered regions), likely to facilitate promiscuous interactions with various target proteins. Unfortunately, however, its interaction with the N-terminal domain of PIAS1 (residues 1-70), which has been identified as one of the CP2b-binding sites, was not observed in the NMR-based titration experiments. Therefore, it could be postulated that the 251-309 region of CP2b would not contact with the PIAS1(1-70), but alternatively interact with another CP2b-binding region that encompasses residues 400-651 of PIAS1.