Article
Biology
Jack Rhodes, Andra-Octavia Roman, Marta Bjornson, Benjamin Brandt, Paul Derbyshire, Michele Wyler, Marc W. Schmid, Frank L. H. Menke, Julia Santiago, Cyril Zipfel
Summary: This study reports on a previously uncharacterised family of plant signalling peptides, CTNIPs, and identifies the orphan receptor HSL3 as their receptor. The HSL3-CTNIP signalling module is conserved in most extant angiosperms. This discovery is important for understanding the diverse functions of plant signalling peptides and receptor-ligand co-evolution.
Article
Biochemistry & Molecular Biology
Nan Wu, Sophia N. Yaliraki, Mauricio Barahona
Summary: Allostery is a common mechanism that regulates protein activity and has great potential for drug design and screening. However, there are few effective computational methods available for predicting allosteric sites, identifying signaling pathways involved in allostery, and aiding in the design of molecules targeting such sites.
JOURNAL OF MOLECULAR BIOLOGY
(2022)
Article
Nanoscience & Nanotechnology
Zhong Guo, Oleh Smutok, Cagla Ergun Ayva, Patricia Walden, Jake Parker, Jason Whitfield, Claudia E. Vickers, Jacobus P. J. Ungerer, Evgeny Katz, Kirill Alexandrov
Summary: The construction and assembly of artificial allosteric protein switches into information and energy processing networks connected to both biological and non-biological systems is a central goal of synthetic biology and bionanotechnology. However, designing protein switches with the desired input, output and performance parameters is challenging. The study demonstrates the design and functionality of YES gate protein switches with large dynamic ranges and fast response rates.
NATURE NANOTECHNOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Chiara Francavilla, Ciara S. O'Brien
Summary: FGFR signaling is critical in breast cancer progression, and its dysregulation can lead to treatment resistance. Understanding the roles of FGFR and its ligands may offer novel treatment strategies for breast cancer patients.
Article
Multidisciplinary Sciences
Qian Wang, Dehai Li, Guangchao Cao, Qiping Shi, Jing Zhu, Mingyue Zhang, Hao Cheng, Qiong Wen, Hao Xu, Leqing Zhu, Hua Zhang, Rachel J. Perry, Olga Spadaro, Yunfan Yang, Shengqi He, Yong Chen, Baocheng Wang, Guangqiang Li, Zonghua Liu, Caixian Yang, Xiaoli Wu, Libing Zhou, Qinghua Zhou, Zhenyu Ju, Hongyun Lu, Yongjie Xin, Xiaoyong Yang, Cunchuan Wang, Yong Liu, Gerald I. Shulman, Vishwa Deep Dixit, Ligong Lu, Hengwen Yang, Richard A. Flavell, Zhinan Yin
Summary: Studies have shown that IL-27 plays a critical role in improving thermogenesis, countering obesity, and ameliorating insulin resistance, making it a promising target for anti-obesity immunotherapy.
Article
Biochemistry & Molecular Biology
Abel Sousa, Aurelien Dugourd, Danish Memon, Borgthor Petursson, Evangelia Petsalaki, Julio Saez-Rodriguez, Pedro Beltrao
Summary: Genetic alterations in cancer cells lead to dysregulation of kinase and transcription factor activities, contributing to oncogenic transformation. We analyzed genomics and (phospho)proteomics data from a large cohort of tumors and cell lines to estimate activity changes in hundreds of kinases and transcription factors. We found co-regulation of kinase and TF activities, revealing known regulatory relationships and dissecting genetic drivers of signaling changes in cancer. Our study also identified differentially regulated activities in cancer subtypes and their association with patient survival, providing insights into the dysregulation of protein activities and its impact on disease severity in cancer.
MOLECULAR SYSTEMS BIOLOGY
(2023)
Review
Plant Sciences
Christina Kronauer, Simona Radutoiu
Summary: Legumes have evolved LysM receptors for recognition of rhizobial Nod factors, crucial for initiating signaling pathways for nodule organogenesis and infection. Recent studies have focused on molecular determinants of specificity and sensitivity in Nod factor signaling, presenting new insights for engineering applications.
CURRENT OPINION IN PLANT BIOLOGY
(2021)
Review
Endocrinology & Metabolism
William J. Smiles, Luca Catalano, Victoria E. Stefan, Daniela D. Weber, Barbara Ko
Summary: Neuroblastoma is a complex paediatric malignancy. ALK, PIM, and Aurora kinases play important roles in neuroblastoma progression and treatment resistance. Intervention in tumor metabolism, especially cellular energy metabolism, through the use of specific kinase inhibitors as part of the treatment regimen, may help overcome treatment resistance.
MOLECULAR METABOLISM
(2023)
Review
Plant Sciences
Mark T. Waters, David C. Nelson
Summary: Karrikins (KARs) are compounds found in smoke that stimulate seed germination and regulate various developmental processes in plants. They are evolutionarily related to strigolactones (SLs) and share similarities in signaling systems. The understanding of KAR/KL signaling has advanced significantly, but there are still unanswered questions and controversies in this field.
Article
Biochemistry & Molecular Biology
Jisu Park, Hyunwoo Choi, Young Doo Kim, Seo-Hyun Kim, Youbin Kim, Youngdae Gwon, Dong Young Lee, Sung-Hye Park, Won Do Heo, Yong-Keun Jung
Summary: The study reveals that aberrantly activated anaplastic lymphoma kinase (ALK) is a key factor contributing to the pathology of Alzheimer's disease (AD), by inducing abnormal accumulation of tau protein and causing dysfunction in neurons. The research demonstrates that ALK disrupts autophagosome maturation, leading to tau accumulation and aggregation, ultimately resulting in neuronal dysfunction in AD.
MOLECULAR PSYCHIATRY
(2021)
Article
Biochemistry & Molecular Biology
Carlos Riechmann, Peijun Zhang
Summary: Bacterial chemosensory arrays have been a valuable model system for studying in-situ structure determination, showcasing the advancements in cryo-electron tomography (cryoET) over the past decade. Recent breakthroughs have led to an accurately fitted atomistic model for the full-length core signalling unit (CSU) and provided insights into the function of transmembrane receptors involved in signal transduction. In this review, we discuss the achievements of the latest structural advances in bacterial chemosensory arrays and the key developments that have enabled these breakthroughs.
CURRENT OPINION IN STRUCTURAL BIOLOGY
(2023)
Review
Cell Biology
Begona Canovas, Angel R. Nebreda
Summary: The ability of cells to cope with various stressful situations is crucial for survival, with p38 alpha kinase playing a key role in the cellular stress response. Understanding the diversity of p38 alpha substrates, their mechanisms, and their connections to specific cellular functions is important for insights into physiology and pathology. Dysregulation of the p38 alpha pathway has been linked to diseases such as inflammation, immune disorders, and cancer.
NATURE REVIEWS MOLECULAR CELL BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Stephanie M. Robert, Benjamin C. Reeves, Emre Kiziltug, Phan Q. Duy, Jason K. Karimy, M. Shahid Mansuri, Arnaud Marlier, Garrett Allington, Ana B. W. Greenberg, Tyrone DeSpenza Jr, Amrita K. Singh, Xue Zeng, Kedous Y. Mekbib, Adam J. Kundishora, Carol Nelson-Williams, Le Thi Hao, Jinwei Zhang, TuKiet T. Lam, Rashaun Wilson, William E. Butler, Michael L. Diluna, Philip Feinberg, Dorothy P. Schafer, Kiavash Movahedi, Allen Tannenbaum, Sunil Koundal, Xinan Chen, Helene Benveniste, David D. Limbrick Jr, Steven J. Schiff, Bob S. Carter, Murat Gunel, J. Marc Simard, Richard P. Lifton, Seth L. Alper, Eric Delpire, Kristopher T. Kahle
Summary: This article investigates the relationship between immune responses and CSF overproduction in post-infectious hydrocephalus (PIH) and post-hemorrhagic hydrocephalus (PHH) models. The results demonstrate that immune responses triggered by breakdown products lead to excessive CSF production, which can be prevented by immunomodulation.
Article
Cell Biology
Xin Chen, Rongfeng Zhu, Jinjin Zhong, Yongfa Ying, Wenxin Wang, Yating Cao, Hanyi Cai, Xiang Li, Jianwei Shuai, Jiahuai Han
Summary: Researchers used super-resolution microscopy to study the nanoscale structure of cellular necrosomes and discovered rod-shaped mosaic structures formed by RIP1 and RIP3 oligomers. They also revealed the roles and regulatory mechanisms of RIP1 and RIP3 in cell death.
NATURE CELL BIOLOGY
(2022)
Article
Multidisciplinary Sciences
Mingqiang Li, Tiannan Yang, Pan Chen, Yongjun Wang, Ruixue Zhu, Xiaomei Li, Ruochen Shi, Heng-Jui Liu, Yen-Lin Huang, Xiumei Ma, Jingmin Zhang, Xuedong Bai, Long-Qing Chen, Ying-Hao Chu, Peng Gao
Summary: Researchers demonstrate the controlled nucleation and motion of isolated three-fold vertices under an applied electric field. This study sheds light on the dynamic property of independent topological polar structures.
NATURE COMMUNICATIONS
(2022)
Article
Multidisciplinary Sciences
Lucy G. Thorne, Mehdi Bouhaddou, Ann-Kathrin Reuschl, Lorena Zuliani-Alvarez, Ben Polacco, Adrian Pelin, Jyoti Batra, Matthew V. X. Whelan, Myra Hosmillo, Andrea Fossati, Roberta Ragazzini, Irwin Jungreis, Manisha Ummadi, Ajda Rojc, Jane Turner, Marie L. Bischof, Kirsten Obernier, Hannes Braberg, Margaret Soucheray, Alicia Richards, Kuei-Ho Chen, Bhavya Harjai, Danish Memon, Joseph Hiatt, Romel Rosales, Briana L. McGovern, Aminu Jahun, Jacqueline M. Fabius, Kris White, Ian G. Goodfellow, Yasu Takeuchi, Paola Bonfanti, Kevan Shokat, Natalia Jura, Klim Verba, Mahdad Noursadeghi, Pedro Beltrao, Manolis Kellis, Danielle L. Swaney, Adolfo Garcia-Sastre, Clare Jolly, Greg J. Towers, Nevan J. Krogan
Summary: The Alpha variant of SARS-CoV-2 effectively suppresses innate immune responses in airway epithelial cells compared to first-wave isolates, possibly due to increased expression of specific viral antagonist proteins. This enhanced innate immune suppression may increase the likelihood of successful transmission of the Alpha variant and potentially impact in vivo replication and infection duration. Mutations outside the spike coding region, such as those observed in the N and Orf9b regulatory regions, play a crucial role in the adaptation of SARS-CoV-2 variants to humans.
Article
Biotechnology & Applied Microbiology
Cristina Vieitez, Bede P. Busby, David Ochoa, Andre Mateus, Danish Memon, Marco Galardini, Umut Yildiz, Matteo Trovato, Areeb Jawed, Alexander G. Geiger, Michaela Oborska-Oplova, Clement M. Potel, Sibylle C. Vonesch, Chelsea Szu Tu, Mohammed Shahraz, Frank Stein, Lars M. Steinmetz, Vikram G. Panse, Kyung-Min Noh, Mikhail M. Savitski, Athanasios Typas, Pedro Beltrao
Summary: Phosphorylation plays a critical role in regulating various cellular processes, but functional annotations for the majority of discovered phosphosites are lacking. A chemical genetic approach was used to study the functional relevance of phosphosites in yeast, revealing potential functional significance for 42% of the sites. This high-throughput method allows for the functional characterization of individual phosphosites at scale.
NATURE BIOTECHNOLOGY
(2022)
Article
Cell Biology
Jeffrey R. Johnson, David C. Crosby, Judd F. Hultquist, Andrew P. Kurland, Prithy Adhikary, Donna Li, John Marlett, Justine Swann, Ruth Huttenhain, Erik Verschueren, Tasha L. Johnson, Billy W. Newton, Michael Shales, Viviana A. Simon, Pedro Beltrao, Alan D. Frankel, Alexander Marson, Jeffery S. Cox, Oliver Fregoso, John A. T. Young, Nevan J. Krogan
Summary: Viruses remodel host cellular pathways to replicate and evade immune defenses and they do so with limited genomic coding capacity. This study used mass spectrometry-based proteomics to analyze protein abundance and post-translational modifications in response to HIV-1 infection. The results revealed the importance of Aurora kinase activity in HIV-1 infection and identified potential substrates of a degraded phosphatase during infection. Additionally, the study showed that the HIV-1 Vpr protein inhibits histone H1 ubiquitination, leading to DNA repair defects.
Article
Biochemistry & Molecular Biology
Sindhuja Sridharan, Alberto Hernandez-Armendariz, Nils Kurzawa, Clement M. Potel, Danish Memon, Pedro Beltrao, Marcus Bantscheff, Wolfgang Huber, Sara Cuylen-Haering, Mikhail M. Savitski
Summary: Reversible protein phosphorylation is an important mechanism for regulating the (dis)assembly of biomolecular condensates. In this study, the authors combined solubility proteome profiling with phosphoproteomics to identify and quantify phosphosites enriched in soluble or condensate-bound protein subpopulations. They demonstrated that certain phosphosites play a role in modulating protein-RNA interactions and the condensation of specific proteins. This dataset provides valuable insights into the phosphoregulation of biomolecular condensates.
NATURE CHEMICAL BIOLOGY
(2022)
News Item
Biotechnology & Applied Microbiology
David Ochoa, Mohd Karim, Maya Ghoussaini, David G. Hulcoop, Ellen M. McDonagh, Ian Dunham
NATURE REVIEWS DRUG DISCOVERY
(2022)
Article
Cell Biology
David Bradley
Summary: Post-translational modifications (PTMs) are chemical modifications that regulate protein activity and function, and represent a fast mechanism for generating phenotypic diversity and divergence. Despite advances in mass spectrometry for identifying PTM classes, little is known about the selective constraints governing PTM evolution.
CURRENT OPINION IN GENETICS & DEVELOPMENT
(2022)
Review
Biochemistry & Molecular Biology
Inigo Barrio-Hernandez, Pedro Beltrao
Summary: GWAS have led to identification of genetic variants associated with human traits and diseases, paving the way for new drug targets. Protein interaction network-based methods can rank candidate drug targets and identify common cell biology affected across diseases, offering opportunities for drug repurposing and tissue-specific targeting. Future improvements are expected through advances in characterisation of context specific interaction networks and joint analysis of rare and common genetic signals.
CURRENT OPINION IN CHEMICAL BIOLOGY
(2022)
Article
Cell Biology
Grant A. King, Rahel Wettstein, Joseph M. Varberg, Keerthana Chetlapalli, Madison E. Walsh, Ludovic C. J. Gillet, Claudia Hernandez-Armenta, Pedro Beltrao, Ruedi Aebersold, Sue L. Jaspersen, Joao Matos, Elcin Unal
Summary: King and Wettstein et al. have discovered that nuclear pore complexes undergo two distinct remodeling events during budding yeast meiosis. This study provides insights into the organization of the nuclear basket and reveals a conserved aspect of NPC plasticity.
JOURNAL OF CELL BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Abel Sousa, Aurelien Dugourd, Danish Memon, Borgthor Petursson, Evangelia Petsalaki, Julio Saez-Rodriguez, Pedro Beltrao
Summary: Genetic alterations in cancer cells lead to dysregulation of kinase and transcription factor activities, contributing to oncogenic transformation. We analyzed genomics and (phospho)proteomics data from a large cohort of tumors and cell lines to estimate activity changes in hundreds of kinases and transcription factors. We found co-regulation of kinase and TF activities, revealing known regulatory relationships and dissecting genetic drivers of signaling changes in cancer. Our study also identified differentially regulated activities in cancer subtypes and their association with patient survival, providing insights into the dysregulation of protein activities and its impact on disease severity in cancer.
MOLECULAR SYSTEMS BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
David F. Burke, Patrick Bryant, Inigo Barrio-Hernandez, Danish Memon, Gabriele Pozzati, Aditi Shenoy, Wensi Zhu, Alistair S. Dunham, Pascal Albanese, Andrew Keller, Richard A. Scheltema, James E. Bruce, Alexander Leitner, Petras Kundrotas, Pedro Beltrao, Arne Elofsson
Summary: In this study, the authors investigate the use of AlphaFold2 to predict protein structures in the human protein-protein interactome and discuss its limitations. They demonstrate the high confidence of the predicted models and identify potential mechanisms for disease mutations. Additionally, they show the application of predicted binary complexes in expanding our understanding of human cell biology.
NATURE STRUCTURAL & MOLECULAR BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Mehmet Akdel, Douglas E. Pires, Eduard Porta Pardo, Jurgen Janes, Arthur O. Zalevsky, Balint Meszaros, Patrick Bryant, Lydia L. Good, Roman A. Laskowski, Gabriele Pozzati, Aditi Shenoy, Wensi Zhu, Petras Kundrotas, Victoria Ruiz Serra, Carlos H. M. Rodrigues, Alistair S. Dunham, David Burke, Neera Borkakoti, Sameer Velankar, Adam Frost, Jerome Basquin, Kresten Lindorff-Larsen, Alex Bateman, Andrey Kajava, Alfonso Valencia, Sergey Ovchinnikov, Janani Durairaj, David B. Ascher, Janet M. Thornton, Norman E. Davey, Amelie Stein, Arne Elofsson, Tristan Croll, Pedro Beltrao
Summary: This study evaluates the performance of AlphaFold2 in structural biology applications and finds that it performs well and can partially replace experimentally determined structures, which is of great significance for life science research.
NATURE STRUCTURAL & MOLECULAR BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
David Ochoa, Andrew Hercules, Miguel Carmona, Daniel Suveges, Jarrod Baker, Cinzia Malangone, Irene Lopez, Alfredo Miranda, Carlos Cruz-Castillo, Luca Fumis, Manuel Bernal-Llinares, Kirill Tsukanov, Helena Cornu, Konstantinos Tsirigos, Olesya Razuvayevskaya, Annalisa Buniello, Jeremy Schwartzentruber, Mohd Karim, Bruno Ariano, Ricardo Esteban Martinez Osorio, Javier Ferrer, Xiangyu Ge, Sandra Machlitt-Northen, Asier Gonzalez-Uriarte, Shyamasree Saha, Santosh Tirunagari, Chintan Mehta, Juan Maria Roldan-Romero, Stuart Horswell, Sarah Young, Maya Ghoussaini, DavidG Hulcoop, Ian Dunham, EllenM McDonagh
Summary: The Open Targets Platform is an open-source resource that facilitates drug target identification and prioritization using publicly available data. It has been redesigned and rebuilt to improve data integration, expand the ways users can explore the data, and enhance the user experience. The platform now includes enhanced gene-disease evidence, new features for assessing target safety and tractability, and machine learning applications for extracting knowledge from literature, clinical trials, and drug labels.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Genetics & Heredity
Inigo Barrio-Hernandez, Jeremy Schwartzentruber, Anjali Shrivastava, Noemi del-Toro, Asier Gonzalez, Qian Zhang, Edward Mountjoy, Daniel Suveges, David Ochoa, Maya Ghoussaini, Glyn Bradley, Henning Hermjakob, Sandra Orchard, Ian Dunham, Carl A. Anderson, Pablo Porras, Pedro Beltrao
Summary: Interacting proteins with similar functions influence organismal traits. Network-based expansion of trait-associated genes for 1,002 human traits recovers known disease genes or drug targets, identifies groups of traits with shared genetic and biological processes, and uncovers pleiotropic gene modules associated with multiple traits. This study demonstrates potential opportunities for drug repurposing and development.
