Article
Multidisciplinary Sciences
Jing Zhao, Alan Blayney, Xiaorong Liu, Lauren Gandy, Weihua Jin, Lufeng Yan, Jeung-Hoi Ha, Ashley J. Canning, Michael Connelly, Chao Yang, Xinyue Liu, Yuanyuan Xiao, Michael S. Cosgrove, Sozanne R. Solmaz, Yingkai Zhang, David Ban, Jianhan Chen, Stewart N. Loh, Chunyu Wang
Summary: Epigallocatechin gallate (EGCG) in green tea induces apoptosis in cancerous cells through a direct interaction with the tumor suppressor p53, inhibiting p53 ubiquitination by its regulatory E3 ligase MDM2 and stabilizing p53 for anti-tumor activity.
NATURE COMMUNICATIONS
(2021)
Article
Biochemistry & Molecular Biology
Salome Araujo-Abad, Jose L. Neira, Bruno Rizzuti, Pilar Garcia-Morales, Camino de Juan Romero, Patricia Santofimia-Castano, Juan Iovanna
Summary: The nuclear protein 1 (NUPR1) and its paralogue nuclear protein 1-like (NUPR1L) are intrinsically disordered proteins involved in stress-mediated cellular conditions. They interact with peptidyl-arginine deiminase 4 (PADI4) in vitro and in cellulo, and the binding regions have been identified. The NUPR1/PADI4 complex may play important roles in DNA repair, metastasis, and protein citrullination.
JOURNAL OF MOLECULAR BIOLOGY
(2023)
Article
Multidisciplinary Sciences
Jie Heng, Yunfei Hu, Guillermo Perez-Hernandez, Asuka Inoue, Jiawei Zhao, Xiuyan Ma, Xiaoou Sun, Kouki Kawakami, Tatsuya Ikuta, Jienv Ding, Yujie Yang, Lujia Zhang, Sijia Peng, Xiaogang Niu, Hongwei Li, Ramon Guixa-Gonzalez, Changwen Jin, Peter W. Hildebrand, Chunlai Chen, Brian K. Kobilka
Summary: Research reveals the dynamic behavior of the beta 2 adrenergic receptor C-terminus and its autoinhibitory function in downstream Gs coupling.
NATURE COMMUNICATIONS
(2023)
Article
Biochemical Research Methods
Jordane Preto, Isabelle Krimm
Summary: The voltage-dependent anion channel (VDAC) is a critical membrane protein in the mitochondrial outer membrane that regulates ion and ATP transport while playing a key role in apoptosis. The N-terminus of VDAC is an intrinsically disordered region that significantly impacts its gating mechanism, providing new insights into the dynamics of the channel.
PLOS COMPUTATIONAL BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Patricia Santofimia-Castano, Bruno Rizzuti, Angel L. Pey, Maria Esther Farez-Vidal, Juan L. Iovanna, Jose L. Neira
Summary: Plakophilin 1 (PKP1) and NUPR1 were found to interact in the nucleus of cells, potentially playing a role in carcinogenesis through modulation of PKP1 function. The binding affinity between PKP1 and NUPR1 was determined to be in the low micromolar range, involving specific typtophan residues of PKP1.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2021)
Article
Biology
Khanh Dinh Quoc Nguyen, Michael Vigers, Eric Sefah, Susanna Seppala, Jennifer Paige Hoover, Nicole Star Schonenbach, Blake Mertz, Michelle Ann O'Malley, Songi Han
Summary: The intrinsically disordered C-terminus of the human adenosine A(2A) receptor (A(2A)R) is found to be a prominent driving factor for receptor homo-oligomerization. A(2A)R oligomer formation decreases progressively with the shortening of the C-terminus, with multiple interaction types contributing to the oligomerization, including disulfide linkages, hydrogen bonds, electrostatic interactions, and hydrophobic interactions. These interactions are enhanced by depletion interactions, creating a tunable network of bonds for A(2A)R oligomers to adopt multiple interfaces.
Article
Biochemistry & Molecular Biology
Salome Araujo-Abad, Maria Fuentes-Baile, Bruno Rizzuti, J. Fernando Bazan, Adrian Villamarin-Ortiz, Miguel Saceda, Eduardo Fernandez, Miguel Vidal, Olga Abian, Adrian Velazquez-Campoye, Camino de Juan Romero, Jose L. Neira
Summary: RYBP is a multifunctional IDP involved in transcriptional regulation, while PADI4 is a well-folded protein implicated in arginine conversion. Both proteins were found to associate in the nucleus and cytosol of cancer cells, suggesting a potential role in cancer development and progression.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2023)
Article
Biochemistry & Molecular Biology
Jung Min Kim, Baik Lin Seong, Jinho Jung
Summary: This study developed a method to label intrinsically disordered native proteins (IDNPs) in mammalian cells while preserving their active structures. By using pure fluorescent methionine and ATTO 565-biotin, IDNPs were labeled at the N- or C-terminus and their concentrations were detected using Ni-NTA beads. The study also demonstrated double labeling of genetically encoded fluorescent-Tat expression using a single fluorescent dye pair and FRET ratio and two-color correlation analysis. This research aims to address native protein processing and achieve ultrasensitive protein folding for nanoscale biological and ecological applications.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2023)
Article
Cell Biology
Assaf Biran, Nadav Myers, Shirel Steinberger, Julia Adler, Marianna Riutin, Karin Broennimann, Nina Reuven, Yosef Shaul
Summary: The degradation of intrinsically disordered proteins (IDPs) by non-26S proteasome process does not necessarily require polyubiquitin targeting. However, it is still unknown how IDPs are recognized by the non-26S proteasome, including the 20S complex. The study discovers that the 20S proteasome subunit, PSMA3, specifically interacts with numerous IDPs. The C-terminus of PSMA3 is found to be an IDP trapper, blocking IDP degradation by the 20S proteasome in vitro.
Article
Multidisciplinary Sciences
Qiao-Hong Chen, V. V. Krishnan
Summary: This study introduces a rational drug discovery strategy based on intrinsically disordered proteins (IDP), defining a differential binding score (DIBS) to quantitatively determine the binding preferences of ligands to different conformations of IDP. By conducting ensemble docking procedures on repeated sampling of conformations, preferential ligand binding sites of IDP can be determined, making this a valuable screening tool for IDP-based drug discovery.
SCIENTIFIC REPORTS
(2021)
Article
Biochemistry & Molecular Biology
Hana Popelka, Vikramjit Lahiri, Wayne D. Hawkins, Felipe da Veiga Leprevost, Alexey I. Nesvizhskii, Daniel J. Klionsky
Summary: The intrinsically disordered protein region (IDPR) of Atg12 protein plays an important role in its functional structure, as it is positioned in proximity to the ubiquitin-like (UBL) domain. Deletion in IDPR disrupts the integrity of the UBL domain, while a mutation in the predicted α0 helix in IDPR prevents Atg12 from binding to Atg7 and Atg10, impacting its function in the ubiquitin-like conjugation cascade.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Joel M. Sowders, Jeremy B. Jewell, Diwaker Tripathi, Kiwamu Tanaka
Summary: P2K1 is a specific purinoceptor in plants that detects extracellular ATP (eATP), a signaling molecule involved in various physiological processes. The C-terminal intrinsically disordered region (IDR) of P2K1 plays a significant role in root growth regulation, as observed by the complete cessation of primary root growth when the IDR is absent. Additionally, a truncated variant of P2K1 lacking the IDR amplifies the response to eATP, leading to superoxide accumulation, altered cell wall integrity, and cell death in the primary root tip.
Article
Multidisciplinary Sciences
William A. McFadden, Judith A. Yanowitz
Summary: Intrinsically disordered proteins (IDPs) and intrinsically disordered regions (IDRs) are flexible peptides that can adopt multiple conformations, providing unique advantages for biological processes. The 'idpr' package in R integrates computational tools for the analysis of IDPs, facilitating the analysis of these important yet under-characterized proteins.
Article
Biochemistry & Molecular Biology
Jing Zhao, Xinyue Liu, Alan Blayney, Yumeng Zhang, Lauren Gandy, Paige Olivia Mirsky, Nathan Smith, Fuming Zhang, Robert J. Linhardt, Jianhan Chen, Christopher Baines, Stewart N. Loh, Chunyu Wang
Summary: The mitochondrial permeability transition pore (mPTP) plays crucial roles in various diseases. Cyclophilin D is confirmed as the only component of mPTP. Previous studies have reported that p53 interacts with CypD through its DNA-binding domain (DBD). However, this study found that the N-terminal domain (NTD) of p53 is the major binding site for CypD. The study provides insights into the dynamic interface between NTD and CypD.
JOURNAL OF MOLECULAR BIOLOGY
(2022)
Article
Biochemical Research Methods
Lei Yu, Rafael Bruschweiler
Summary: The article investigates the molecular simulation of two intrinsically disordered proteins (IDPs) and validates them with experimental data. The results show that the new molecular dynamics simulation method can generate highly realistic protein conformational ensembles, which are of great significance for understanding the biological function of IDPs.
PLOS COMPUTATIONAL BIOLOGY
(2022)