Review
Chemistry, Multidisciplinary
Matti Mar, Kateryna Nitsenko, Petur O. Heidarsson
Summary: Eukaryotic transcription factors play a crucial role in integrating molecular feedback and regulating gene expression. They consist of structured DNA-binding domains and long intrinsically disordered regions (IDRs). The dynamic multifunctionality of IDRs is essential for their functions in genome regulation. This review analyzes the chemical features of TF IDRs and their involvement in protein interactions, DNA binding, chromatin opening, and phase separation. Suggestions are given for future research to integrate experiments and simulations in understanding TF functions.
CHEMISTRY-A EUROPEAN JOURNAL
(2023)
Article
Biochemistry & Molecular Biology
Xi Wang, Harry M. Greenblatt, Lavi S. Bigman, Binhan Yu, Channing C. Pletka, Yaakov Levy, Junji Iwahara
Summary: This study investigates how D/E repeats cause autoinhibition of HMGB1 and its specific binding to cisplatin-modified DNA. By varying ionic strength, the conformational equilibrium between autoinhibited and uninhibited states can be shifted, revealing fuzzy interactions of D/E repeats with other intrinsically disordered regions. Mutations mimicking post-translational modifications relevant to nuclear export of HMGB1 can moderately modulate DNA-binding affinity, possibly by impacting the autoinhibition.
JOURNAL OF MOLECULAR BIOLOGY
(2021)
Article
Biology
Raghavendar R. Sanganna Gari, Grigory Tagiltsev, Ruth A. Pumroy, Yining Jiang, Martin Blackledge, Vera Y. Moiseenkova-Bell, Simon Scheuring
Summary: This study used high-speed atomic force microscopy to image TRPV2 channels in membranes and found that the N-terminal intrinsically disordered regions (IDRs) were involved in intermolecular interactions. The results provide evidence about the 'structure' of TRPV2 IDRs and suggest their potential role in mediating protein-protein interactions.
COMMUNICATIONS BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Mariane Goncalves-Kulik, Pablo Mier, Kristina Kastano, Juan Cortes, Pau Bernado, Friederike Schmid, Miguel A. Andrade-Navarro
Summary: This study provides evidence that low complexity regions (LCRs) within intrinsically disordered regions (IDRs) of proteins can induce local structure. By predicting IDRs in the human proteome and analyzing structures in the Protein Data Bank (PDB), the researchers found that LCRs were more likely to have structural information assigned to them compared to surrounding IDRs. The most frequent LCRs containing E (Glu) or G (Gly) were found to induce helical or coil structures. These findings suggest a structuring role of LCRs within IDRs.
Article
Biochemistry & Molecular Biology
Xi Wang, Lavi S. Bigman, Harry M. Greenblatt, Binhan Yu, Yaakov Levy, Junji Iwahara
Summary: This study investigates the mechanism by which D/E repeats in DNA/RNA-binding proteins accelerate the target search process, using experimental and simulation approaches.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Jaime Santos, Irantzu Pallares, Valentin Iglesias, Salvador Ventura
Summary: The prevalence of cryptic amyloidogenic regions (CARs) of polar nature in intrinsically disordered regions (IDRs) has been explored. CARs are associated with protein function and interactions, but also carry a risk of malfunction. The existence of ancestral CARs may have evolved into functional interacting regions, playing a significant role in protein evolution at the origins of life.
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2021)
Article
Biochemistry & Molecular Biology
Christopher M. Furman, Ting-Yi Wang, Qiuye Zhao, Kumar Yugandhar, Haiyuan Yu, Eric Alani
Summary: This study demonstrated that dynamic and coordinated rearrangements of the MLH IDRs regulate the function of the MLH complex positively and negatively in MMR.
NUCLEIC ACIDS RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Samuel R. Witus, Lisa M. Tuttle, Wenjing Li, Alex Zelter, Meiling Wang, Klaiten E. Kermoade, Damien B. Wilburn, Trisha N. Davis, Peter S. Brzovic, Weixing Zhao, Rachel E. Klevit
Summary: BRCA1/BARD1 is a tumor suppressor gene with functions in DNA damage repair and transcriptional regulation. It interacts with nucleosomes and facilitates ubiquitylation of histone H2A. Our study reveals novel interactions involving an intrinsically disordered DNA-binding region of BARD1 that support H2A ubiquitylation and recruitment to chromatin and DNA damage sites. These interactions contribute to cell survival and identify a network of BARD1-nucleosome interactions on chromatin.
Article
Biochemistry & Molecular Biology
Shangbo Ning, Hong-Jun Chao, Shuangli Li, Rui Zhou, Lei Zou, Xu Zhang, Jun Liu, Dazhong Yan, Mojie Duan
Summary: This study investigates the molecular mechanism of phosphorylation regulation on the auto-inhibition of Ets-1 using molecular simulations and biochemical experiments. The results suggest that both steric hindrance and allosteric regulation are involved in the DNA-binding inhibitory effect caused by phosphorylation, with steric effects playing a greater role.
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2022)
Article
Biochemistry & Molecular Biology
Karen E. Lee, Rebecca Procopio, Jose S. Pulido, Kammi B. Gunton
Summary: Intrinsically disordered regions (IDRs) are protein regions that lack stable tertiary structures and play important roles in signaling and regulation through dynamic interactions. Understanding IDRs and their association with biological function may shed light on the development of inherited retinal diseases (IRDs). This study aims to investigate the level of disorder in 14 proteins related to IRDs and its correlation with the number of pathogenic missense variants.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Biochemistry & Molecular Biology
John J. Ferrie, Jonathan P. Karr, Robert Tjian, Xavier Darzacq
Summary: There are differences in structure and function between bacterial and eukaryotic transcription factors, and the intrinsically disordered regions in eukaryotic transcription factors play a crucial role in their interactions with other proteins and chromatin. Understanding the role of disordered regions is essential for a deep understanding of the regulatory mechanisms of eukaryotic transcription factors.
Article
Biochemistry & Molecular Biology
Gozde Kibar, Martin Vingron
Summary: Protein-protein interactions (PPIs) are crucial for molecular processes, but the mechanisms of molecular recognition between interacting proteins are poorly understood, making it challenging to predict interactions from sequence. This study proposes a new method using intrinsically disordered regions (IDRs) to tackle this challenge. Using IDR sequences, the researchers predicted PPIs in candidate proteins and divided the prediction problem into subproblems, adapting appropriate strategies. The findings highlight the importance of defining problem type and suggest that accounting for IDRs can aid in predicting features of the intrinsically disordered protein interaction network, accelerating efforts to understand the eukaryotic PPI network.
PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS
(2023)
Review
Biochemistry & Molecular Biology
Denisa Jamecna, Bruno Antonny
Summary: Membrane contact sites are regions of close apposition between membrane-bound organelles, where proteins, including lipid transfer proteins, display various domain organization. Intrinsic disordered protein regions play multiple roles in LTPs, such as serving as flexible tethers between membranes, entropic barriers, and defining the action range of catalytic domains. These functions, along with mediating protein-protein and protein-membrane interactions, require fine coordination for the efficiency and fidelity of contact sites.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS
(2021)
Article
Biochemistry & Molecular Biology
Carlos Pintado-Grima, Oriol Barcenas, Zoe Manglano-Artunedo, Rita Vilaca, Sandra Macedo-Ribeiro, Irantzu Pallares, Jaime Santos, Salvador Ventura
Summary: Proteome-wide analyses have revealed that amyloidogenic regions are present in most globular proteins, while being underrepresented in intrinsically disordered proteins (IDPs). However, recent research has shown that intrinsically disordered regions (IDRs) do contain significant amyloid load in the form of cryptic amyloidogenic regions (CARs), which are exposed to solvent and are more polar than conventional amyloid regions. CARs are associated with both IDPs function and malfunction, and their presence is linked to pathologies such as cancer and Alzheimer's disease. To explore these previously unnoticed amyloidogenic regions, CARs-DB, a database containing precomputed predictions for all CARs in the IDPs deposited in the DisProt database, was developed. CARs-DB allows for easy access to a large number of unique CARs and has been validated by demonstrating the amyloidogenic potential of selected CARs.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2022)
Review
Biochemistry & Molecular Biology
Amit Chaudhary, Pankaj Kumar Chaurasia, Sandeep Kushwaha, Pallavi Chauhan, Aakash Chawade, Ashutosh Mani
Summary: Cold shock proteins are a conserved family of proteins that play important roles in low-temperature stress response and nucleic acid binding in bacteria. They are involved in various cellular and metabolic processes in prokaryotes and have been found to be crucial in the progression of cancer and Alzheimer's disease in humans.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2022)