Review
Biochemistry & Molecular Biology
Amita R. Sahoo, Matthias Buck
Summary: This review focuses on the interaction between Eph receptors and ephrin ligands in regulating various processes from embryonic development to tissue homeostasis. It also highlights the importance of the transmembrane domain of Eph receptors in signal transduction and introduces techniques such as NMR and molecular modeling used to study them. Additionally, the use of transmembrane peptides to manipulate Eph receptor signaling is discussed, along with future directions for research in this field.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Multidisciplinary Sciences
Xiao Teng, Sijia Chen, Qing Wang, Zhao Chen, Xiaoying Wang, Niu Huang, Sanduo Zheng
Summary: G protein-coupled receptors (GPCRs) are the largest family of membrane receptors and the most important drug targets. This study reports the structures of the D1 dopamine receptor and mini-G(s) complex, providing insights into the molecular mechanisms of G protein activation.
Article
Hematology
Louris J. Feitsma, Harma C. Brondijk, Gavin E. Jarvis, Dominique Hagemans, Dominique Bihan, Natasia Jerah, Marian Versteeg, Richard W. Farndale, Eric G. Huizinga
Summary: Glycoprotein VI (GPVI) plays a crucial role in collagen-induced platelet activation and is essential in the development of thrombosis, heart attack, and stroke. This study reveals the crystal structures of GPVI bound to collagen peptides and identifies the binding site and essential residues for collagen binding. The study also demonstrates the binding of GPVI to collagen chains containing the sequence motif OGPOGP. These findings provide insights for the development of receptor-specific therapeutics targeting GPVI.
Article
Multidisciplinary Sciences
Gyunghee Jo, Jeomil Bae, Ho Jeong Hong, Ah-reum Han, Do-Kyun Kim, Seon Pyo Hong, Jung A. Kim, Sangkyu Lee, Gou Young Koh, Ho Min Kim
Summary: Angiopoietin (Angpt)-Tie receptor 2 (Tie2) plays a key role in regulating vascular stability and is a potential therapeutic target in vascular diseases. A new Tie2-agonistic antibody has been developed, targeting a site distinct from the Angpt1-binding site, influencing Tie2 clustering and activation in an Angpt2 inhibition-resistant manner.
NATURE COMMUNICATIONS
(2021)
Article
Multidisciplinary Sciences
Ashish Kumar, Reafa A. Hossain, Samantha A. Yost, Wei Bu, Yuanyuan Wang, Altaira D. Dearborn, Arash Grakoui, Jeffrey Cohen, Joseph Marcotrigiano
Summary: The study shows that low pH enhances the binding of CD81-LEL to E2, leading to a conformational change in E2 in preparation for membrane fusion.
Review
Biochemistry & Molecular Biology
Yuanfa Yao, Jianxu Li, Yinyan Lin, Jiaqiang Zhou, Peng Zhang, Yingke Xu
Summary: This review summarizes the sequences and structures of different species of PLD isoforms, and discusses the structural mechanisms for PLD interactions with their binding partners and the functions of each key domain in regulating PLDs activation and catalytic reaction.
PROGRESS IN LIPID RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Nelly Morellet, Pierre Hardouin, Nadine Assrir, Carine van Heijenoort, Beatrice Golinelli-Pimpaneau
Summary: This study investigates the structural organization of Bacillus subtilis RNase Y using NMR and AlphaFold models. The N-terminal domain of RNase Y is found to have a long coiled-coil structure connected to a C-terminal region composed of helices. The structural organization of the N-terminal domain is maintained in the full-length model of RNase Y, and the C-terminal region is likely involved in the dimerization of RNase Y.
Article
Multidisciplinary Sciences
Shichen Su, Jia Wang, Ting Deng, Xun Yuan, Jinqiu He, Nan Liu, Xiaomin Li, Ying Huang, Hong-Wei Wang, Jinbiao Ma
Summary: This study revealed the molecular mechanism for the full cycle of ATP-dependent dsRNA processing by Dcr-2-Loqs-PD. The structures of Dcr-2-Loqs-PD in various states during dsRNA processing were determined using cryo-electron microscopy. The study elucidated the conformational changes and interactions between Dcr-2 and Loqs-PD, providing insights into the RNA interference mechanism and potential therapeutic strategies for related diseases.
Article
Biochemistry & Molecular Biology
Nirupa Nagaratnam, Silvia L. Delker, Rebecca Jernigan, Thomas E. Edwards, Janey Snider, Darren Thifault, Dewight Williams, Brent L. Nannenga, Mary Stofega, Lidia Sambucetti, James J. Hsieh, Andrew J. Flint, Petra Fromme, Jose M. Martin-Garcia
Summary: Taspase1 is an Ntn-hydrolase overexpressed in primary human cancers, with its activity closely related to the proliferation, invasion, and metastasis of cancer cells. This study reveals the structure and function of the active site of Taspase1, providing a potential target for the development of anticancer therapeutics.
Article
Biology
Florian Bleffert, Joachim Granzin, Muttalip Caliskan, Stephan N. Schott-Verdugo, Meike Siebers, Bjoern Thiele, Laurence Rahme, Sebastian Felgner, Peter Doermann, Holger Gohlke, Renu Batra-Safferling, Karl-Erich Jaeger, Filip Kovacic
Summary: Cells adapt their membrane composition to changing conditions by regulating GPL synthesis and degradation. This study identified a cytoplasmic membrane-bound phospholipase A(1) (PlaF) from Pseudomonas aeruginosa that might be involved in GPL remodeling. PlaF is an important virulence factor and its structure and activation mechanism were revealed, offering insights for the development of therapeutics targeting PlaF.
Article
Biochemistry & Molecular Biology
Ayesha Zaka, Maha Yousaf, Shaheen Shahzad, Hadi Zahid Rao, Jia Nee Foo, Saima Siddiqi
Summary: 3M syndrome is a rare genetic familial disorder characterized by short stature, growth retardation, facial dysmorphism, skeletal abnormalities, fleshy protruding heels, and normal intelligence, caused by mutations in the CUL7, OBSL1 and CCDC8 genes. In this study, a novel homozygous missense variant of CUL7 has been identified in a consanguineous Pakistani family. Computational and experimental investigations reveal that this variant alters the protein's structure and interaction, providing useful information for drug development against this syndrome.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Article
Biochemistry & Molecular Biology
Budheswar Dehury, Sarbani Mishra, Sanghamitra Pati
Summary: The spread of different SARS-CoV-2 variants highlights the importance of understanding the structural properties of its proteins. This study reveals the structural dynamics of M-PRO, an attractive drug target for antiviral treatments, and identifies stable and compact conformations with intact catalytic sites and structural integrity.
JOURNAL OF CELLULAR BIOCHEMISTRY
(2023)
Review
Pharmacology & Pharmacy
David Machalz, Szymon Pach, Marcel Bermudez, Matthias Bureik, Gerhard Wolber
Summary: This review summarizes recent structural insights into understudied cytochrome P450 enzymes, highlighting the impact of molecular modeling for mechanistically explaining pathophysiological effects and establishing understudied CYPs as promising drug targets.
DRUG DISCOVERY TODAY
(2021)
Article
Biochemistry & Molecular Biology
F. Xavier Gomis-Rueth, Walter Stoecker
Summary: Astacins are a family of metallopeptidases found in animals, consisting of multidomain extracellular proteins. They share similar structural features with other metallopeptidases and belong to the metzincin metallopeptidase clan. The distribution and origin of astacins have been investigated, and it is proposed that they originated in the root of Holozoa through horizontal gene transfer.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2023)
Article
Multidisciplinary Sciences
Florian Altegoer, Tessa E. F. Quax, Paul Weiland, Phillip Nussbaum, Pietro Giammarinaro, Megha Patro, Zhengqun Li, Dieter Oesterhelt, Martin Grininger, Sonja-Verena Albers, Gert Bange
Summary: Signal transduction via phosphorylated CheY is conserved in bacteria and archaea. In this study, the authors employ structural biochemistry combined with cell biology to delineate the mechanism of CheY recognition by the adaptor protein CheF.
NATURE COMMUNICATIONS
(2022)
Review
Cell Biology
Song Gao, Junjie Hu
Summary: Mitochondria are dynamic organelles that undergo fusion and fission, which can impact their function and lead to diseases. Fusion of outer and inner mitochondrial membranes is mediated by dynamin-like proteins, but the molecular mechanisms behind this process remain unclear despite recent structural studies.
TRENDS IN CELL BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Liming Yan, Ji Ge, Litao Zheng, Ying Zhang, Yan Gao, Tao Wang, Yucen Huang, Yunxiang Yang, Shan Gao, Mingyu Li, Zhenyu Liu, Haofeng Wang, Yingjian Li, Yu Chen, Luke W. Guddat, Quan Wang, Zihe Rao, Zhiyong Lou
Summary: The study presents a structural snapshot of SARS-CoV-2 RTC during mRNA transcription, revealing the interaction between nsp9 and nsp12, as well as the catalytic activity of nsp12 NiRAN. The results demonstrate an intermediate state of RTC towards mRNA synthesis, providing valuable information for antiviral drug development.
Article
Chemistry, Multidisciplinary
Xiangyang Guo, Jan Steinkuehler, Mariana Marin, Xiang Li, Wuyuan Lu, Rumiana Dimova, Gregory B. Melikyan
Summary: IFITM3 inhibits the transition from hemifusion to full fusion by inducing negative membrane curvature and increasing membrane order and stiffness, thus blocking the entry of diverse enveloped viruses.
Article
Biochemistry & Molecular Biology
Jin Wang, Lei Li, Zhenhua Ming, Lijie Wu, Liming Yan
Summary: The tubules of endoplasmic reticulum (ER) spread into yeast buds through an actin-based mechanism and become attached to the proteinaceous micro-compartment called polarisome. The minimal tether between polarisome and cortical ER is formed by a protein complex consisting of Epo1, Scs2, and Cdc42 guanosine triphosphatase-activating protein Bem3. This study presents the crystal structure of the complex between Epo1 and Bem3, providing a structural insight into the link between cortical ER and polarisome.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Cell Biology
Fang Chen, Bing Yan, Jie Ren, Rui Lyu, Yanfang Wu, Yuting Guo, Dong Li, Hong Zhang, Junjie Hu
Summary: FIT2 interacts with ER tubule-forming proteins and septin 7 to facilitate nascent LD biogenesis. Depletion of these proteins leads to a decrease in the number and size of LDs within cells.
JOURNAL OF CELL BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Liming Yan, Yunxiang Yang, Mingyu Li, Ying Zhang, Litao Zheng, Ji Ge, Yucen C. Huang, Zhenyu Liu, Tao Wang, Shan Gao, Ran Zhang, Yuanyun Y. Huang, Luke W. Guddat, Yan Gao, Zihe Rao, Zhiyong Lou
Summary: The study presents the cryo-EM structure of the SARS-CoV-2 replication-transcription complex (RTC) Cap(0)-RTC, demonstrating the proofreading mechanism of nsp14 and the role of nsp10/nsp14 in the formation of the capping complex.
Article
Biochemistry & Molecular Biology
Meng Yang, Asigul Ismayil, Zhihao Jiang, Yan Wang, Xiyin Zheng, Liming Yan, Yiguo Hong, Dawei Li, Yule Liu
Summary: The study reveals that the replicase gamma a of Barley stripe mosaic virus can inhibit vacuolar acidification and suppress autophagic degradation to promote viral infection in plants. The disruption of vacuolar acidification seems to be a common viral counter-defense strategy employed by multiple viruses, highlighting the importance of functional vacuolar acidification in plant antiviral defense.
Article
Multidisciplinary Sciences
Xiao Tang, Rong Chen, Vince St Dollente Mesias, Tingxuan Wang, Ying Wang, Kristina Poljak, Xinyu Fan, Hanchi Miao, Junjie Hu, Liang Zhang, Jinqing Huang, Shuhuai Yao, Elizabeth A. Miller, Yusong Guo
Summary: Sonic Hedgehog (Shh) is a signaling molecule that plays crucial roles in mammalian development. This study investigates the mechanisms underlying the secretion of the N-terminal fragment of Shh (ShhN). The findings reveal the involvement of the ON motif and SURF4 in the ER-to-Golgi transport of ShhN, and the competition between PGs and SURF4 for binding to ShhN in the Golgi.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Cell Biology
Liqing Liu, Shuxin Yang, Yang Liu, Xixia Li, Junjie Hu, Li Xiao, Tao Xu
Summary: In this study, a tool called DeepContact was developed for optimizing organelle segmentation and contact analysis using label-free electron microscopy (EM) through deep learning algorithms. DeepContact showed high efficiency and flexibility, capable of accommodating various organelle morphologies and identifying contacts of different widths. The study revealed previously unidentified coordinated rearrangements of organelles and a subtle wave of interaction between the endoplasmic reticulum (ER) and mitochondria in Sertoli cells during the seminiferous epithelial cycle, demonstrating the potential of DeepContact in bridging MCS dynamics to physiological and pathological processes.
JOURNAL OF CELL BIOLOGY
(2022)
Article
Medicine, Research & Experimental
Zhigang Wang, Yuanbo Qi, Yonghua Feng, Hongen Xu, Junxiang Wang, Luyu Zhang, Jie Zhang, Xinyue Hou, Guiwen Feng, Wenjun Shang
Summary: The levels of m6A and WTAP are elevated in CD4+ T cells of tolerant kidney transplant recipients. WTAP facilitates Foxo1 transcription by enhancing m6A modification of Foxo1 mRNA in the CDS region, leading to Treg cell differentiation and function. Overexpression of WTAP alleviates allograft rejection in model mice. These findings suggest the positive role of WTAP in immune tolerance induction post kidney transplant.
LABORATORY INVESTIGATION
(2022)
Article
Biochemistry & Molecular Biology
Liming Yan, Yucen Huang, Ji Ge, Zhenyu Liu, Pengchi Lu, Bo Huang, Shan Gao, Junbo Wang, Liping Tan, Sihan Ye, Fengxi Yu, Weiqi Lan, Shiya Xu, Feng Zhou, Lei Shi, Luke W. Guddat, Yan Gao, Zihe Rao, Zhiyong Lou
Summary: This study reveals the mechanism of SARS-CoV-2 RNA capping and provides atomic resolution structural details. It shows that the NiRAN domain plays a crucial role in RNAylation and the formation of GpppA. Moreover, triphosphorylated nucleotide analog inhibitors can inhibit RNAylation and GpppA formation by binding to nsp9. The conformational shift of the S-loop in NiRAN observed in the presence of sofosbuvir monophosphate suggests a possible mechanism for designing inhibitors.
Article
Cell Biology
Lu Xu, Yun Xiang, Junjie Hu
Summary: The ER-resident protein Climp63 plays a key role in maintaining the width of cisternal structures in the endoplasmic reticulum (ER) through multi-modular self-association. The LD of Climp63 is highly α-helical, with a five-helix bundle (5HB) module interacting with the C-terminus of the LD to generate a width of -50 nm for ER sheets.
JOURNAL OF CELL SCIENCE
(2023)
Article
Pharmacology & Pharmacy
Yuanbo Qi, Mingyao Hu, Yang Qiu, Luyu Zhang, Yongchuang Yan, Yi Feng, Chenghao Feng, Xinyue Hou, Zhigang Wang, Di Zhang, Jie Zhao
Summary: This study found that thiazolidinedione (TZD) compounds play an important role in ischemia/reperfusion-induced kidney damage, especially its derivative mitoglitazone (MGZ) has significant inhibitory effects. MGZ alleviated cell death and inflammation, upregulated GPX4 expression, and reduced iron-related lipid peroxidation in kidney tissues. Mechanistically, MGZ exhibited a high binding affinity with the mitochondrial outer membrane protein mitoNEET, which mediates the ferroptosis pathway.
TOXICOLOGY AND APPLIED PHARMACOLOGY
(2023)
Correction
Multidisciplinary Sciences
Yun Xiang, Rui Lyu, Junjie Hu
NATURE COMMUNICATIONS
(2023)
Article
Multidisciplinary Sciences
Yun Xiang, Rui Lyu, Junjie Hu
Summary: Membrane curvature is generated by constructing a curved oligomeric scaffold formed by endoplasmic reticulum tubule-forming proteins. The mechanism of curvature generation remains elusive.
NATURE COMMUNICATIONS
(2023)