Article
Dermatology
Chiara Angiolilli, Emmerik F. A. Leijten, Cornelis P. J. Bekker, Ella Eeftink, Barbara Giovannone, Michel Olde Nordkamp, Marlot van der Wal, Judith L. Thijs, Sebastiaan J. Vastert, Femke van Wijk, Timothy R. D. J. Radstake, Jorg van Loosdregt
Summary: Dermal fibroblasts in psoriatic skin are important producers of inflammatory mediators, and their cytokine production is regulated by ZFP36 family members. The expression of ZFP36 family proteins is reduced in chronic inflammatory conditions that mimic psoriatic skin.
JOURNAL OF INVESTIGATIVE DERMATOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Caitlin Walker, Yingjie Wang, Cristina Olivieri, V. S. Manu, Jiali Gao, David A. Bernlohr, Davide Calebiro, Susan S. Taylor, Gianluigi Veglia
Summary: Somatic mutations in the PRKACA gene lead to the development of Cushing's syndrome, with the E31V allosteric mutation disrupting communication nodes and nucleotide-substrate binding cooperativity. The loss of binding cooperativity in Cushing's syndrome mutants is proportional to the density of the intramolecular allosteric network, suggesting a common mechanism for this disease.
JOURNAL OF MOLECULAR BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Yun-Sang Tang, Shutong Xu, Yu-Wai Chen, Jia-Huai Wang, Pang-Chui Shaw
Summary: This study revealed the binding mechanism between H5N1 influenza virus nucleoprotein and RNA nucleotides, confirming the importance of flexible loops and the C-terminal tail in RNA binding, and proposing a mechanism by which NP captures and transfers RNA.
NUCLEIC ACIDS RESEARCH
(2021)
Article
Microbiology
Jayanti Singh, Ruchi Anand, Amnon Horovitz
Summary: The NtrC family of AAA+ proteins are bacterial transcriptional regulators that respond to phenol and play a role in the degradation of phenol. MopR, a member of this family, undergoes concentration-dependent oligomerization and is regulated by phenol binding, shifting its equilibrium to a derepressed state with low-affinity for ATP. These findings provide insights into the allosteric regulation of MopR and can be applied to the study of other AAA+ proteins.
JOURNAL OF BACTERIOLOGY
(2022)
Article
Oncology
Parag P. P. Shah, Levi J. J. Beverly
Summary: The UBQLN family of proteins, including UBQLN1 and UBQLN2, has important regulatory roles in cancer progression and tumorigenesis. Loss of UBQLN1/UBQLN2 leads to increased cell viability, proliferation, migration, clonogenic potential, and cell cycle progression, which is associated with increased MYC expression. UBQLN1 and UBQLN2 interact with phosphorylated MYC and facilitate its degradation. Overexpression of UBQLN1 reverses the increased expression of MYC following the loss of UBQLN2. Loss of UBQLN1 drives tumorigenesis and lung metastasis in mice, which is associated with increased expression of MYC, proteins involved in cell cycle progression, and EMT. These findings suggest a novel role of UBQLN1 and UBQLN2 in regulating MYC in lung adenocarcinoma cells.
Article
Plant Sciences
Veronica M. Beretta, Emanuela Franchini, Israr Ud Din, Elia Lacchini, Lisa Van den Broeck, Rosangela Sozzani, Gregorio Orozco-Arroyo, Elisabetta Caporali, Helene Adam, Stefan Jouannic, Veronica Gregis, Martin M. Kater
Summary: The architecture of the rice inflorescence plays a crucial role in determining crop yield. The timing of the transition from branch meristem to spikelet meristem affects the complexity of the inflorescence. Two ALOG genes, OsG1L1 and OsG1L2, show expression profiles similar to TAW1 and their loss-of-function mutants have similar phenotypes. Transcriptome analysis led to the construction of a gene regulatory network, which identified OsHOX14 as a potential protein involved in rice inflorescence development.
Article
Biochemistry & Molecular Biology
Natasha J. Freidman, Chelsea Briot, Renae M. Ryan
Summary: This study found that the compound GPNA can activate the Cl- conductance of ASCT2 without undergoing the transport cycle. This is a previously unreported phenomenon for inhibitors of the solute carrier 1A family. Additionally, GPNA was found to inhibit several excitatory amino acid transporters. These findings raise questions about the anticancer mechanisms of GPNA.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Cell Biology
Miryam Mueller, Claire Saunders, Anke Senftleben, Johannes P. W. Heidbuechel, Birgit Halwachs, Julia Bolik, Nina Hedemann, Christian Roeder, Dirk Bauerschlag, Stefan Rose-John, Dirk Schmidt-Arras
Summary: Tspan8 subfamily members regulate the substrate selectivity of ADAM17 through different strategies, especially by recruiting ADAM17 into Tspan-enriched micro-domains to promote ADAM17-mediated TNF alpha release. This finding reveals the mechanism of Tspan8's involvement in tumorigenesis.
Article
Plant Sciences
Zhen Wang, Zai Zheng, Yumin Zhu, Shuyao Kong, Dong Liu
Summary: To understand the molecular mechanism of plant transcriptional responses to phosphate (Pi) starvation, this study investigated the function of PHR1 and its homologs PHL1, PHL2, and PHL3 in Arabidopsis. The results showed that PHR1/PHL1 and PHL2/PHL3 function as two separate modules in regulating plant development and transcriptional responses to Pi starvation. PHR1 plays a dominant role in the PHR1/PHL1 module, while PHL2 and PHL3 contribute similarly in the PHL2/PHL3 module. The study also identified the common and specific targets of these PHR proteins and revealed their role as both positive and negative regulators of Pi starvation-responsive gene expression.
Article
Medicine, Research & Experimental
Ryosuke Hiwa, Hailyn Nielsen, James L. Mueller, Ravi Mandla, Julie Zikherman
Summary: The NR4A family of orphan nuclear receptors plays redundant roles in establishing and maintaining Treg identity, and deletion of family members leads to Treg deficiency and severe inflammatory diseases. Through a competitive bone marrow chimera strategy, it was discovered that DKO bone marrow chimeras developed autoantibodies and inflammatory diseases despite having a Treg compartment mostly from WT origin. This study highlights the essential cell intrinsic roles of the NR4A family in central and peripheral T cell tolerance, demonstrating their importance in immune homeostasis.
Article
Microbiology
Xiaoxu Ma, Lixin Lu, Youmin Zhang, Ming Fang, Kaisheng Shao, Xu Sun, Fangjie Yao, Peng Wang
Summary: This study revealed the genetic control mechanism of color traits in A. cornea through genetic analysis. It found that the color trait is controlled by two pairs of alleles. By constructing a genetic linkage map, the study finely mapped the color-controlling genetic locus and validated the interaction between genes, proteins, and phenotypes, uncovering the mechanism of pigment synthesis inhibition in A. cornea.
Article
Cell Biology
David Liang, Liping Jiang, Sameer Ahmed Bhat, Sonia Missiroli, Mariasole Perrone, Angela Lauriola, Ritika Adhikari, Anish Gudur, Zahra Vasi, Ian Ahearn, Daniele Guardavaccaro, Carlotta Giorgi, Mark Philips, Shafi Kuchay
Summary: This study reveals that the interplay of two lipid modifications and PDE68 regulates the targeting of substrates in specific membrane compartments via SCFFBXL2. The distribution of FBXL2 within the cell is regulated by palmitoylation/depalmitoylation, which affects substrate degradation. Interaction with PDE68 also plays a role in regulating its distribution. Disrupting the balance between FBXL2 and PDE68 prevents FBXL2 from reaching all membrane compartments, while depalmitoylated FBXL2 accumulates on the endoplasmic reticulum and promotes the degradation of IP3R3.
Review
Biochemistry & Molecular Biology
Mi Kyung Park, Ho Lee, Chang Hoon Lee
Summary: This review article provides an overview of the diverse functions of PTM in protein regulation and the pivotal role of ZEB family transcription factors in tumour progression and metastasis. The article also discusses the PTM of ZEBs and potential therapeutic approaches.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Qiming Liu, Shouzhen Teng, Chen Deng, Suting Wu, Haoshu Li, Yanwei Wang, Jinxia Wu, Xuean Cui, Zhiguo Zhang, William Paul Quick, Thomas P. Brutnell, Xuehui Sun, Tiegang Lu
Summary: C-3 and C-4 grasses are crucial for human diet, but our understanding of the molecular mechanisms driving photosynthesis in these grasses is limited. A genetic circuit involving SHR, IDD, and PIN family members controls vein formation and ground cell proliferation in leaves of both C-3 and C-4 grasses. This circuit regulates auxin transport through negative regulation of PIN expression and plays a role in minor vein patterning in grasses.
Review
Medicine, Research & Experimental
Siyu Zhang, Yuxin Tong
Summary: In this review, we summarize the structure, post-translational modifications, and cellular pathways regulated by SoHo family proteins, with a focus on ArgBP2. We also discuss the significance of SoHo family proteins in cellular distribution, extracellular matrix microenvironments, and drug discovery.
BIOMEDICINE & PHARMACOTHERAPY
(2022)
Article
Multidisciplinary Sciences
Daniel-Adriano Silva, Shawn Yu, Umut Y. Ulge, Jamie B. Spangler, Kevin M. Jude, Carlos Labao-Almeida, Lestat R. Ali, Alfredo Quijano-Rubio, Mikel Ruterbusch, Isabel Leung, Tamara Biary, Stephanie J. Crowley, Enrique Marcos, Carl D. Walkey, Brian D. Weitzner, Fatima Pardo-Avila, Javier Castellanos, Lauren Carter, Lance Stewart, Stanley R. Riddell, Marion Pepper, Goncalo J. L. Bernardes, Michael Dougan, K. Christopher Garcia, David Baker
Article
Biochemical Research Methods
Julia Koehler Leman, Brian D. Weitzner, Steven M. Lewis, Jared Adolf-Bryfogle, Nawsad Alam, Rebecca F. Alford, Melanie Aprahamian, David Baker, Kyle A. Barlow, Patrick Barth, Benjamin Basanta, Brian J. Bender, Kristin Blacklock, Jaume Bonet, Scott E. Boyken, Phil Bradley, Chris Bystroff, Patrick Conway, Seth Cooper, Bruno E. Correia, Brian Coventry, Rhiju Das, Rene M. De Jong, Frank DiMaio, Lorna Dsilva, Roland Dunbrack, Alexander S. Ford, Brandon Frenz, Darwin Y. Fu, Caleb Geniesse, Lukasz Goldschmidt, Ragul Gowthaman, Jeffrey J. Gray, Dominik Gront, Sharon Guffy, Scott Horowitz, Po-Ssu Huang, Thomas Huber, Tim M. Jacobs, Jeliazko R. Jeliazkov, David K. Johnson, Kalli Kappel, John Karanicolas, Hamed Khakzad, Karen R. Khar, Sagar D. Khare, Firas Khatib, Alisa Khramushin, Indigo C. King, Robert Kleffner, Brian Koepnick, Tanja Kortemme, Georg Kuenze, Brian Kuhlman, Daisuke Kuroda, Jason W. Labonte, Jason K. Lai, Gideon Lapidoth, Andrew Leaver-Fay, Steffen Lindert, Thomas Linsky, Nir London, Joseph H. Lubin, Sergey Lyskov, Jack Maguire, Lars Malmstroem, Enrique Marcos, Orly Marcu, Nicholas A. Marze, Jens Meiler, Rocco Moretti, Vikram Khipple Mulligan, Santrupti Nerli, Christoffer Norn, Shane O'Conchuir, Noah Ollikainen, Sergey Ovchinnikov, Michael S. Pacella, Xingjie Pan, Hahnbeom Park, Ryan E. Pavlovicz, Manasi Pethe, Brian G. Pierce, Kala Bharath Pilla, Barak Raveh, P. Douglas Renfrew, Shourya S. Roy Burman, Aliza Rubenstein, Marion F. Sauer, Andreas Scheck, William Schief, Ora Schueler-Furman, Yuval Sedan, Alexander M. Sevy, Nikolaos G. Sgourakis, Lei Shi, Justin B. Siegel, Daniel-Adriano Silva, Shannon Smith, Yifan Song, Amelie Stein, Maria Szegedy, Frank D. Teets, Summer B. Thyme, Ray Yu-Ruei Wang, Andrew Watkins, Lior Zimmerman, Richard Bonneau
Article
Multidisciplinary Sciences
Sarju Adhikari, Ramon Crehuet, Josep M. Anglada, Joseph S. Francisco, Yu Xia
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2020)
Article
Biochemical Research Methods
Giulio Tesei, Joao M. Martins, Micha B. A. Kunze, Yong Wang, Ramon Crehuet, Kresten Lindorff-Larsen
Summary: DEER-PREdict is a software program designed to predict distance distributions and relaxation enhancement rates of proteins from ensembles of protein conformations. It efficiently operates on large conformational ensembles, with demonstrated performance and accuracy in experimentally characterized protein systems such as HIV-1 protease and T4 Lysozyme. The open-source program combines molecular modeling and simulations with experiments to provide useful tools for interpreting experimental results and validating molecular models of flexible proteins.
PLOS COMPUTATIONAL BIOLOGY
(2021)
Article
Polymer Science
Agusti Emperador, Ramon Crehuet, Elvira Guardia
Summary: The study found that TIP4P/2005 is the only water model that accurately simulates the fast association/dissociation dynamics of ubiquitin protein and accurately identifies its binding surface, highlighting the critical role of water models in describing protein self-association processes.
Article
Biochemistry & Molecular Biology
Anders Lonstrup Hansen, Johanna M. Koivisto, Signe Simonsen, Zehui Dong, Ramon Crehuet, Dennis K. Hansen, Martin Willemoes
Summary: The study identified the importance of Asp-682 and a conserved water molecule in the activation of the catalytic nucleophile in endo-alpha-N-acetylgalactosaminidase EngBF. Mutagenesis experiments showed that His-685, His-718, and the catalytic water molecule are also crucial for catalytic activity.
Article
Multidisciplinary Sciences
Giulio Tesei, Thea K. Schulze, Ramon Crehuet, Kresten Lindorff-Larsen
Summary: Researchers have found that many intrinsically disordered proteins (IDPs) can participate in the formation of membraneless organelles in the cell. Investigating the phase behavior of IDPs through molecular simulations requires an accurate description of intramolecular and intermolecular interactions. By developing a coarse-grained model based on experimental data, the model accurately reproduces the conformational propensities of IDPs.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Biology
Nicolai Tidemand Johansen, Marta Bonaccorsi, Tone Bengtsen, Andreas Haahr Larsen, Frederik Gronbaek Tidemand, Martin Cramer Pedersen, Pie Huda, Jens Berndtsson, Tamim Darwish, Nageshewar Rao Yepuri, Anne Martel, Thomas Gunther Pomorski, Andrea Bertarello, Mark Sansom, Mikaela Rapp, Ramon Crehuet, Tobias Schubeis, Kresten Lindorff-Larsen, Guido Pintacuda, Lise Arleth
Summary: This study investigates the conformation and dynamic behavior of the Mg2+ channel CorA using small-angle neutron scattering, molecular dynamics simulations, and solid-state nuclear magnetic resonance spectroscopy. The researchers find that CorA undergoes conformational equilibria between multiple states and that conducting states become more populated in the absence of Mg2+. These findings are crucial for understanding the functional regulation of CorA.
Article
Biochemistry & Molecular Biology
Soraia R. Mendes, Ulrich Eckhard, Arturo Rodriguez-Banqueri, Tibisay Guevara, Peter Czermak, Enrique Marcos, Andreas Vilcinskas, F. Xavier Gomis-Ruth
Summary: The insect metallopeptidase inhibitor (IMPI) produced by Galleria mellonella has been found to inhibit the pathogenic bacterium Staphylococcus aureus, which may contribute to the development of novel protein drugs for treating Staphylococcus aureus infections.
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2022)
Article
Multidisciplinary Sciences
Tamuka M. Chidyausiku, Soraia R. Mendes, Jason C. Klima, Marta Nadal, Ulrich Eckhard, Jorge Roel-Touris, Scott Houliston, Tibisay Guevara, Hugh K. Haddox, Adam Moyer, Cheryl H. Arrowsmith, F. Xavier Gomis-Ruth, David Baker, Enrique Marcos
Summary: The researchers develop design rules for tailoring immunoglobulin domains and demonstrate their ability to accurately design these domains de novo with high stability and the ability to scaffold functional loops.
NATURE COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Daniel Penas-Utrilla, Enrique Marcos
Summary: Computational de novo protein design tailors proteins for specific functions by leveraging design data and protein structure prediction advances, allowing for more accurate selection of promising designs for experimental testing.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2022)
Correction
Multidisciplinary Sciences
Kerry Blair, Muhammad Tehseen, Vlad-Stefan Raducanu, Taha Shahid, Claudia Lancey, Fahad Rashid, Ramon Crehuet, Samir M. Hamdan, Alfredo De Biasio
NATURE COMMUNICATIONS
(2023)
Article
Multidisciplinary Sciences
Kerry Blair, Muhammad Tehseen, Vlad-Stefan Raducanu, Taha Shahid, Claudia Lancey, Fahad Rashid, Ramon Crehuet, Samir M. Hamdan, Alfredo De Biasio
Summary: Using cryo-EM structures and functional assays, we have discovered the mechanism of action of DNA Ligase 1 (Lig1) and the sliding clamp PCNA in lagging strand synthesis. Lig1 recruits PCNA to nicked DNA using specific PCNA-interacting motifs, and facilitates substrate handoff from FEN1 for ligation. Additionally, PCNA forms a defined complex with FEN1 and nicked DNA, and recruits Lig1 for DNA transfer.
NATURE COMMUNICATIONS
(2022)
Article
Multidisciplinary Sciences
Jorge Roel-Touris, Marta Nadal, Enrique Marcos
Summary: This study presents principles for de novo designing single-chain immunoglobulin dimers with interfaces diverging from those seen in antibodies. The designed protein scaffolds are stable and capable of accommodating multiple functional loops. This architecture shows enhanced stability and both robustness and modularity for harboring multiple functional loops.
NATURE COMMUNICATIONS
(2023)
Meeting Abstract
Biophysics
Albert Escobedo, Busra Topal, Micha Kunze, Juan Aranda, Giulio Chiesa, Bahareh Eftekharzadeh, Roberta Pierattelli, Isabella C. Felli, Tammo Diercks, Oscar Millet, Jesus Garcia, Modesto Orozco, Ramon Crehuet, Kresten Lindorff-Larsen, Xavier Salvatella
BIOPHYSICAL JOURNAL
(2020)