Article
Multidisciplinary Sciences
Sarah A. Mosure, Timothy S. Strutzenberg, Jinsai Shang, Paola Munoz-Tello, Laura A. Solt, Patrick R. Griffin, Douglas J. Kojetin
Summary: Heme is an endogenous ligand for REV-ERB nuclear receptors, regulating their activity by binding with corepressor NCoR and influencing the thermodynamic interaction profile between NCoR and REV-ERBβ. This finding sheds light on the mechanism of heme-dependent REV-ERB activity.
Article
Biochemistry & Molecular Biology
Krishna Mohan Sepuru, Krishna Rajarathnam
Summary: Chemokines Cxcl1 and Cxcl2 play crucial roles in neutrophil migration, with their recruitment activity regulated by GAGs; Cxcl1 and Cxcl2 can form heterodimers, exhibiting different binding characteristics to free and immobilized GAGs, as well as from homodimers, regulating chemokine function.
BIOCHEMICAL JOURNAL
(2021)
Article
Chemistry, Multidisciplinary
Nam Gu Yoon, Hakbong Lee, So-Yeon Kim, Sung Hu, Darong Kim, Sujae Yang, Ki Bum Hong, Ji Hoon Lee, Soosung Kang, Byung-Gyu Kim, Kyungjae Myung, Changwook Lee, Byoung Heon Kang
Summary: The study identified Mitoquinone (MitoQ) as a potent inhibitor of mitochondrial Hsp90, offering potential anticancer properties. By competitively binding with TRAP1 clients, MitoQ facilitated the identification of mitochondrial protein interactions. Targeting the client binding site of Hsp90 family proteins provides a novel strategy for developing potent anticancer drugs.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2021)
Article
Biology
Georgios I. Laliotis, Adam D. Kenney, Evangelia Chavdoula, Arturo Orlacchio, Abdul Kaba, Alessandro La Ferlita, Vollter Anastas, Christos Tsatsanis, Joal D. Beane, Lalit Sehgal, Vincenzo Coppola, Jacob S. Yount, Philip N. Tsichlis
Summary: AKT-phosphorylated IWS1 promotes the alternative splicing of U2AF2, leading to regulation of mRNA nuclear export, including those encoding Type I interferons. This pathway affects sensitivity to multiple cytolytic virus infections, and may serve as a potential therapeutic target in cancer treatment.
COMMUNICATIONS BIOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Sankhadip Bhadra, Yong-jie Xu
Summary: The heterotrimeric Tel2-Tti1-Tti2 or TTT complex is essential for cell viability and widely observed in eukaryotes. It plays crucial roles in genome stability, cell proliferation, telomere maintenance, and aging as the co-chaperone of several important proteins. TTT interacts with Hsp90 through the R2TP complex or other proteins to facilitate the co-translational maturation of PIKKs. Mutations of the TTT can cause disease syndromes and its misregulation is associated with multiple cancers. Tel2 in the TTT complex has been found to be a target of the antiparasitic drug ivermectin, suggesting its potential use for cancer chemotherapy.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Multidisciplinary Sciences
Benoit Bragantini, Christophe Charron, Maxime Bourguet, Arnaud Paul, Decebal Tiotiu, Benjamin Rothe, Helene Marty, Guillaume Terral, Steve Hessmann, Laurence Decourty, Marie-Eve Chagot, Jean-Marc Strub, Severine Massenet, Edouard Bertrand, Marc Quinternet, Cosmin Saveanu, Sarah Cianferani, Stephane Labialle, Xavier Manival, Bruno Charpentier
Summary: Biogenesis of eukaryotic box C/D small nucleolar ribonucleoproteins involves various assembly machinery components and genetic interactions with chromatin organization factors. Bcd1p regulates the recruitment of histone chaperone Rtt106p by modulating its association with RNA polymerase II and levels of H3K56ac. The study provides evidence for a protein interaction interface for Rtt106p that controls its transcription-associated activity, and suggests a link between ribosome formation and chromatin functions.
NATURE COMMUNICATIONS
(2021)
Article
Biology
Kangcheng Song, Miao Wei, Wenjun Guo, Li Quan, Yunlu Kang, Jing-Xiang Wu, Lei Chen
Summary: TRPC5 channel is a nonselective cation channel involved in various physiological processes. Inhibitors of TRPC5, such as clemizole and HC-070, stabilize the ion channel in a nonconductive closed state, potentially offering new therapeutic strategies for anxiety disorders, depression, and kidney diseases. The cryo-EM structures of human TRPC5 with inhibitors provide insights into the binding sites and inhibitory mechanisms, facilitating the development of more effective inhibitors targeting TRPC5.
Article
Multidisciplinary Sciences
Diane Heiser, Joelle Rubert, Adeline Unterreiner, Claudine Maurer, Marion Kamke, Ursula Bodendorf, Christopher J. Farady, Ben Roediger, Frederic Bornancin
Summary: PKD activation precedes cleavage of caspase-1 and gasdermin D, and inhibition of PKD can block NLRP3 inflammasome assembly and IL-1β production. However, PKD's promiscuous reactivity challenges its potential use for tracing the NLRP3 inflammasome pathway.
Review
Biochemistry & Molecular Biology
Brady M. Owen, Chen Davidovich
Summary: Polycomb group proteins contribute to the targeting of PRCs to chromatin through DNA-binding activities, but the specific mechanisms of CpG island targeting cannot be fully explained by DNA sequence alone.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Multidisciplinary Sciences
Qin Gong, Kim Robinson, Chenrui Xu, Phuong Thao Huynh, Kelvin Han Chung Chong, Eddie Yong Jun Tan, Jiawen Zhang, Zhao Zhi Boo, Daniel Eng Thiam Teo, Kenneth Lay, Yaming Zhang, John Soon Yew Lim, Wah Ing Goh, Graham Wright, Franklin L. Zhong, Bruno Reversade, Bin Wu
Summary: NLRP1 and CARD8 are two recently characterized sensor proteins for the human inflammasome complex. The cryo-EM CARD filament structures of the NLRP1 and CARD8 activating domains reveal how NLRP1 and CARD8 discriminate between ASC and pro-caspase-1. The authors propose a two-step model for NLRP1 activation.
NATURE COMMUNICATIONS
(2021)
Article
Oncology
Dan Song, Ming Guo, Shuai Xu, Xiaotian Song, Bin Bai, Zhengyan Li, Jie Chen, Yanxin An, Yongzhan Nie, Kaichun Wu, Shiqi Wang, Qingchuan Zhao
Summary: PUS7 is overexpressed in colorectal cancer tissues, associated with advanced clinical stages and shorter overall survival. Silencing PUS7 effectively inhibits CRC cell metastasis, while upregulation promotes metastasis independently of its catalytic activity. The HSP90/PUS7/LASP1 axis may represent a novel therapeutic approach for CRC.
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
(2021)
Article
Chemistry, Multidisciplinary
Yinan Wang, Mingxi Yao, Karen B. Baker, Rosemarie E. Gough, Shimin Le, Benjamin T. Goult, Jie Yan
Summary: This study quantifies the kinetics of force-dependent talin-vinculin interactions and reveals a new regulatory mechanism in which mechanically exposed VBS binds vinculin more tightly. Molecular dynamics simulations provide insight into the force-dependent conformational changes in the VBS that modulate binding. Overall, the interplay between force and autoinhibition adds complexity to the major mechanosensing axis involving talin and vinculin.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2021)
Article
Multidisciplinary Sciences
Juan Manuel Valverde, Geronimo Dubra, Michael Phillips, Austin Haider, Carlos Elena-Real, Aurelie Fournet, Emile Alghoul, Dhanvantri Chahar, Nuria Andres-Sanchez, Matteo Paloni, Pau Bernado, Guido van Mierlo, Michiel Vermeulen, Henk van den Toorn, Albert J. R. Heck, Angelos Constantinou, Alessandro Barducci, Kingshuk Ghosh, Nathalie Sibille, Puck Knipscheer, Liliana Krasinska, Daniel Fisher, Maarten Altelaar
Summary: This study provides insight into the molecular mechanisms and kinetics of mitotic cellular reorganisation by analyzing the dynamics of protein phosphorylation in the vertebrate cell cycle. The authors show that protein phosphorylation is largely regulated by cyclin-dependent kinases (CDKs) and involves intrinsically disordered proteins that are responsible for biomolecular condensate formation.
NATURE COMMUNICATIONS
(2023)
Article
Oncology
Yi Ding, Zehua Wang, Chen Chen, Dongyu Li, Wenjia Wang, Yongxu Jia, Yanru Qin
Summary: This study found that KLK11 is downregulated in gastric cancer and reduces the proliferative capacity of gastric cancer cells by inhibiting the phosphorylation of mTOR/4E-BP1. On the other hand, miR-1304 promotes gastric cancer cell proliferation by inhibiting KLK11. KLK11 can also limit the proliferation of gastric cancer cells in vivo.
Article
Biochemistry & Molecular Biology
Eleanor Glancy, Claudio Ciferri, Adrian P. Bracken
Summary: PRC2 is a crucial chromatin complex essential for cellular development and identity maintenance, catalyzing different levels of methylation on histone H3. These activities may be dysregulated in cancer and certain developmental disorders. Through the coordination of core and accessory proteins, PRC2 faithfully deposits H3K27 methylations genome-wide.
CURRENT OPINION IN STRUCTURAL BIOLOGY
(2021)
Article
Multidisciplinary Sciences
Federica Schiavoni, Pedro Zuazua-Villar, Theodoros Roumeliotis, Graeme Benstead-Hume, Mercedes Pardo, Frances M. G. Pearl, Jyoti S. Choudhary, Jessica A. Downs
Summary: Aneuploidy causes a decrease in cellular fitness, but it is commonly found in cancer cells and often associated with aggressive growth, indicating that the impact of aneuploidy on cellular fitness depends on the context. In this study, the loss of the BRG1 subunit of the SWI/SNF chromatin remodeling complex is shown to enable tolerance to aneuploidy. This creates an environment where chromosomal changes can occur without a fitness penalty, allowing adaptation to changing environments. This may play a significant role in the progression of BRG1-deficient cancers.
NATURE COMMUNICATIONS
(2022)
Review
Biochemistry & Molecular Biology
Chrisostomos Prodromou, Dennis M. Bjorklund
Summary: Hsp90, an ATP molecular chaperone, plays a crucial role in the activation and maturation of client proteins. Recent studies have shed light on the mechanism of Hsp90, including its ATP hydrolysis and the remodeling of client proteins for their activation.
Article
Biology
Chloe R. Koulouris, Sian E. Gardiner, Tessa K. Harris, Karen T. Elvers, S. Mark Roe, Jason A. Gillespie, Simon E. Ward, Olivera Grubisha, Robert A. Nicholls, John R. Atack, Benjamin D. Bax
Summary: Human serine racemase (hSR) catalyzes the conversion of L-serine to D-serine and plays a role in the activation of NMDA receptors. The positioning of Tyr121 appears to be crucial in regulating the activity of hSR.
COMMUNICATIONS BIOLOGY
(2022)
Article
Cell Biology
Hugang Feng, Karen A. Lane, Theodoros Roumeliotis, Penny A. Jeggo, Navita Somaiah, Jyoti S. Choudhary, Jessica A. Downs
Summary: PBRM1 deficiency is associated with the response to immunotherapy in renal cancer, potentially through DNA damage-induced inflammatory signaling and maintenance of the G2/M checkpoint. The mutational status of PBRM1 can predict the response of renal cancer to immunotherapy.
GENES & DEVELOPMENT
(2022)
Article
Biochemistry & Molecular Biology
Matthew Day, Antony W. Oliver, Laurence H. Pearl
Summary: The RAD9-RAD1-HUS1 (9-1-1) clamp is part of the DNA damage checkpoint system that can detect large regions of single-stranded DNA caused by replication fork collapse or DNA double-strand breaks. A study using cryogenic electron microscopy reveals the structure of the human RAD17-RFC clamp loader complex bound to human 9-1-1 at a dsDNA-ssDNA junction, providing insight into how RAD17 confers specificity for 9-1-1 and how the clamp loader recognizes the recessed 5' DNA end and orients 9-1-1 on the ssDNA.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Dennis M. Bjorklund, R. Marc L. Morgan, Jasmeen Oberoi, Katie L. I. M. Day, Panagiota A. Galliou, Chrisostomos Prodromou
Summary: The study identified the interaction between CDC37 and BRAF and determined the crucial structural elements of CDC37 involved in BRAF recognition. The dimerization of BRAF can inhibit the recognition by CDC37, and the consequences of BRAF mutations on signaling were discussed.
Article
Chemistry, Organic
Storm Hassell-Hart, Elisa Speranzini, Sirihathai Srikwanjai, Euan Hossack, S. Mark Roe, Daren Fearon, Daniel Akinbosede, Stephen Hare, John Spencer
Summary: A library of thiazoles and selenothiazoles were synthesized via Ir-catalyzed ylide insertion chemistry. This process is tolerant to functional groups and heterocycle substituents, making it applicable for the synthesis of anti-inflammatory drugs and enzyme-binding compounds in bacteria.
Article
Multidisciplinary Sciences
V. U. Chukhutsina, J. M. Baxter, A. Fadini, R. M. Morgan, M. A. Pope, K. Maghlaoui, C. M. Orr, A. Wagner, J. J. van Thor
Summary: This study provides insights into the photo-sensing mechanism of Orange Carotenoid protein (OCP), revealing the involvement of single bond isomerization and structural changes. The findings contribute to a better understanding of OCP's role in light-harvesting.
NATURE COMMUNICATIONS
(2022)
Article
Multidisciplinary Sciences
Jasmeen Oberoi, Xavi Aran-Guiu, Emily A. Outwin, Pascale Schellenberger, Theodoros Roumeliotis, Jyoti S. Choudhary, Laurence H. Pearl
Summary: Binding to HSP90-CDC37 is crucial for the activity of protein kinases, and the phosphatase PP5 plays a role in dephosphorylating the bound kinase. This study provides insights into the activation and reset mechanism of client protein kinases by the HSP90 molecular chaperone system.
NATURE COMMUNICATIONS
(2022)
Article
Multidisciplinary Sciences
Angel Rivera-Calzada, Raquel Arribas-Bosacoma, Alba Ruiz-Ramos, Paloma Escudero-Bravo, Jasminka Boskovic, Rafael Fernandez-Leiro, Antony W. Oliver, Laurence H. Pearl, Oscar Llorca
Summary: Vaccinia virus uses proteins C4 and C16 to interfere with the host immune response. The authors provide the structural basis for this viral defense mechanism, which is conserved in other poxviruses.
NATURE COMMUNICATIONS
(2022)
Article
Multidisciplinary Sciences
Luke A. Yates, Elias A. Tannous, R. Marc Morgan, Peter M. Burgers, Xiaodong Zhang
Summary: This study reveals the phosphorylation circuit that regulates checkpoint recruitment and function in response to DNA damage. The interaction between Ddc2 and RPA modulates the association between RPA and ssDNA, and phosphorylated Ddc2 enhances its recruitment to RPA-ssDNA, promoting DNA damage checkpoint signaling.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Biology
Amit Kumar, Oscar Vadas, Nicolas Dos Santos Pacheco, Xu Zhang, Kin Chao, Nicolas Darvill, Helena O. Rasmussen, Yingqi Xu, Gloria Meng-Hsuan Lin, Fisentzos A. Stylianou, Jan Skov Pedersen, Sarah L. Rouse, Marc L. Morgan, Dominique Soldati-Favre, Stephen Matthews
Summary: The intracellular parasites belonging to the phylum of Apicomplexa employ substrate-dependent gliding motility to invade host cells. The glideosome-associated connector (GAC), a conserved protein, plays a crucial role in this process. The crystal structure of Toxoplasma gondii GAC reveals a unique armadillo repeat region that adopts a closed ring conformation. The properties of GAC suggest that it can adopt multiple conformations from closed to open and extended, and a multi-conformational model is proposed for its assembly and regulation within the glideosome.
Editorial Material
Biochemistry & Molecular Biology
Chrisostomos Prodromou
Article
Multidisciplinary Sciences
Douglas Sammon, Anja Krueger, Marta Busse-Wicher, Rhodri Marc Morgan, Stuart M. Haslam, Benjamin Schumann, David C. Briggs, Erhard Hohenester
Summary: Heparan sulfate (HS) and chondroitin sulfate (CS) control development and physiology in a specific manner. The modification of core proteins with HS or CS is carried out selectively by N-acetylglucosaminyltransferase EXTL3 and equally by N-acetylgalactosaminyltransferase CSGALNACT2, respectively. Phosphorylation accelerates linker synthesis and the initiation of HS and CS.
NATURE COMMUNICATIONS
(2023)
Article
Chemistry, Multidisciplinary
Khodayar Gholivand, Mohammad Faraghi, Samaneh K. Tizhoush, Sara Ahmadi, Mostafa Yousefian, Fahimeh Mohammadpanah, S. Mark Roe
Summary: Two new Ag(i) complexes were synthesized and fully characterized. One of the complexes showed stronger antibacterial and anticancer activity. The crystal structure and intermolecular interactions of the complexes were studied, and the mechanism of cell death induced by the complexes was evaluated through apoptosis and other experiments.
NEW JOURNAL OF CHEMISTRY
(2022)