Article
Biochemistry & Molecular Biology
Yue Li, Hongda Huang
Summary: The human facilitates chromatin transcription (FACT) complex, composed of Spt16 and SSRP1, can bind to free H2A-H2B dimer and H3-H4 tetramer (or dimer), as well as partially unraveled nucleosome. The C-terminal domain of human Spt16 (hSpt16-CTD) is crucial for the recognition of H2A-H2B dimer and partially unraveled nucleosome. This study reveals the molecular basis of H2A-H2B dimer recognition by hSpt16-CTD through an acidic intrinsically disordered (AID) segment and identifies some unique structural features of hSpt16-CTD compared to yeast Spt16-CTD. (c) 2023 Elsevier Inc. All rights reserved.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2023)
Article
Multidisciplinary Sciences
Khuram U. Ashraf, Rie Nygaard, Owen N. Vickery, Satchal K. Erramilli, Carmen M. Herrera, Thomas H. McConville, Vasileios I. Petrou, Sabrina I. Giacometti, Meagan Belcher Dufrisne, Kamil Nosol, Allen P. Zinkle, Chris L. B. Graham, Michael Loukeris, Brian Kloss, Karolina Skorupinska-Tudek, Ewa Swiezewska, David I. Roper, Oliver B. Clarke, Anne-Catrin Uhlemann, Anthony A. Kossiakoff, M. Stephen Trent, Phillip J. Stansfeld, Filippo Mancia
Summary: This study presents the structures of WaaL from Cupriavidus metallidurans and provides molecular details and a mechanistic model for lipopolysaccharide maturation.
Review
Biochemistry & Molecular Biology
Romualdo Troisi, Nicole Balasco, Ida Autiero, Luigi Vitagliano, Filomena Sica
Summary: In this paper, the structural aspects of protein-aptamer recognition process were reviewed by surveying the content of the Protein Data Bank. The study identified a significant increase in the number of determined structures of protein-aptamer complexes in the last two years. The complex architectures and the molecular mechanism of the binding process were also analyzed.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Bojana Kravic, Tihana Bionda, Alexander Siebert, Pinki Gahlot, Sophie Levantovsky, Christian Behrends, Hemmo Meyer
Summary: LMP is an underlying feature of diverse conditions, and cells respond by ubiquitylation for clearance of the organelle facilitated by the ubiquitin-directed AAA-ATPase VCP/p97. The study discovered a large diversity of targets and lysophagy regulators during acute LMP.
Article
Multidisciplinary Sciences
Yiwei Chen, Kai Xu, Luca Piccoli, Mathilde Foglierini, Joshua Tan, Wenjie Jin, Jason Gorman, Yaroslav Tsybovsky, Baoshan Zhang, Boubacar Traore, Chiara Silacci-Fregni, Claudia Daubenberger, Peter D. Crompton, Roger Geiger, Federica Sallusto, Peter D. Kwong, Antonio Lanzavecchia
Summary: This study demonstrates that Plasmodium falciparum RIFINs can bind to LILRB1 through D3, and inserting receptor domains into the VH-CH1 elbow can generate novel antibodies, as shown by a naturally selected example.
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
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
Chemistry, Multidisciplinary
Hyunsung Nam, Joon Soo An, Jaepil Lee, Yonghwan Yun, Hyunbin Lee, Hyungou Park, Yousung Jung, Ki-Bong Oh, Dong-Chan Oh, Seokhee Kim
Summary: This study demonstrates the ability of cytochrome P450 enzymes to generate diverse biaryl linkages, expanding the chemical diversity of macrocyclic peptides. Using genome mining and NMR structure determination, the study identified three unprecedented or rare biaryl linkages. The findings are significant for exploring the chemical structures of biaryl-containing peptides encoded in bacterial genomes.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
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
Chemistry, Multidisciplinary
Xuefeng Cao, Shuaishuai Wang, Madhusudhan Reddy Gadi, Ding Liu, Peng G. Wang, Xiu-Feng Wan, Jian Zhang, Xi Chen, Lauren E. Pepi, Parastoo Azadi, Lei Li
Summary: This article describes the systematic synthesis of bisected N-glycans and their application in constructing a glycan microarray for studying their recognition by various glycan-binding proteins.
Article
Cell Biology
Huaxin Song, Jiale Wu, Yigang Tang, Yuting Dai, Xinrong Xiang, Ya Li, Lili Wu, Jiaqi Wu, Ying Liang, Yangfei Xing, Ni Yan, Yuntong Li, Zhengyuan Wang, Shujun Xiao, Jiabing Li, Derun Zheng, Xinjie Chen, Hai Fang, Chenjing Ye, Yuting Ma, Yu Wu, Wen Wu, Junming Li, Sujiang Zhang, Min Lu
Summary: In this study, the authors evaluated the rescue abilities of 800 common p53 mutants using the compound arsenic trioxide (ATO). They found that the solvent accessibility and temperature sensitivity of mutated residues were key factors in determining if a mutation could be rescued. A total of 390 mutants were successfully rescued and classified into three types. ATO showed preferential inhibition on type 1 and type 2a mutants in both mouse trials and clinical trials. This study provides a valuable resource for the scientific and clinical communities and proposes a new strategy for targeting p53 based on individual mutant alleles.
SCIENCE TRANSLATIONAL MEDICINE
(2023)
Article
Biochemistry & Molecular Biology
James K. Fields, Chad W. Hicks, Cynthia Wolberger
Summary: Post-translational modification of histones, including methylation and monoubiquitination, plays a crucial role in transcription regulation. Methylation of H3K4 and H3K79 activates transcription, while methylation of H3K27 represses transcription. These modifications are dependent on prior monoubiquitination of specific histone residues, leading to a phenomenon called histone crosstalk. Recent studies have provided new insights into the mechanisms of how these modifications regulate the activity of various histone-modifying enzymes.
CURRENT OPINION IN STRUCTURAL BIOLOGY
(2023)
Article
Multidisciplinary Sciences
Jialiang Wang, Jingdan Liang, Lu Chen, Wei Zhang, Liangliang Kong, Chao Peng, Chen Su, Yi Tang, Zixin Deng, Zhijun Wang
Summary: Statins, effective cholesterol-lowering drugs, depend on a megasynthase complex for biosynthesis. CryoEM structures of LovB-LovC and core LovB provide insights into the catalytic cycle for lovastatin production.
NATURE COMMUNICATIONS
(2021)
Article
Multidisciplinary Sciences
Chang Liu, Wei Shi, Scott T. Becker, David G. Schatz, Bin Liu, Yang Yang
Summary: This study highlights the crucial role of ExoN in the coronavirus life cycle, its recognition and excision of nucleotide analog inhibitors, and provides insight into the molecular mechanisms of mismatch correction during coronavirus RNA synthesis. The cryo-electron microscopy structures reveal the molecular determinants of ExoN substrate specificity, offering guidance for the rational design of improved anticoronavirus therapies.
Review
Cell Biology
Valeria Vasileva, Vladislav Chubinskiy-Nadezhdin
Summary: PIEZO1 is a mechanosensitive channel widely found in eukaryotic organisms. The molecular structure, activation mechanisms, and regulating pathways of PIEZO1 remain open questions. Two hypotheses - force-from-lipids and force-from-filaments - have been proposed to explain PIEZO1 gating. Both lipids and components of the extracellular matrix (ECM) and cytoskeleton have been shown to play important roles in the regulation of PIEZO1 properties. The microenvironment of the channel, including the plasma membrane, cytoskeleton, and ECM, is critical for the functioning of PIEZO1.
JOURNAL OF CELLULAR PHYSIOLOGY
(2023)
Article
Chemistry, Physical
Hasan Cinar, Rosario Oliva, Haowei Wu, Mingjie Zhang, Hue Sun Chan, Roland Winter
Summary: The study reveals the high pressure sensitivity of the SynGAP/PSD-95 system and suggests that deep-sea organisms counteract this sensitivity to avoid neurological impairment. The findings offer insights into the neurological effects of hydrostatic pressure and potential strategies to alleviate pressure-induced neurological disorders.
JOURNAL OF PHYSICAL CHEMISTRY B
(2022)
Article
Chemistry, Physical
Hua-Qi Wang, Shu-Bin Mou, Wen Xiao, Huan Zhou, Xu-Dong Hou, Su-Jing Wang, Qian Wang, Jiali Gao, Zhiyi Wei, Lijun Liu, Zheng Xiang
Summary: CylK is a key enzyme that catalyzes the formation of the cylindrocyclophane scaffold through Friedel-Crafts alkylation reactions, exhibiting regioselectivity and stereospecificity. This study proposes a concerted double-activation mechanism to explain the enzymatic alkylation with regioselectivity and stereospecificity, based on crystal structures, free energy simulations, and site-directed mutagenesis experiments.
Article
Cell Biology
Zhe Feng, Suho Lee, Bowen Jia, Tao Jian, Eunjoon Kim, Mingjie Zhang
Summary: The scaffold protein IRSp53 plays an important role in synapse development and synaptic plasticity. This study reveals that specific interactions between IRSp53 and its binding partners PSD-95 or Shank3 drive phase separation of complexes and promote synaptic enrichment of IRSp53 in mouse cortical neurons. The study also highlights the role of IRSp53 in actin filament formation and synaptic maturation. These findings provide mechanistic insights into the physiological roles of IRSp53 in synapse formation and function.
JOURNAL OF CELL BIOLOGY
(2022)
Article
Multidisciplinary Sciences
Yingdong Shi, Lin Lin, Chao Wang, Jinwei Zhu
Summary: The research reveals that Gpsm2 undergoes phase separation and the Gpsm2-G alpha i complex contributes to the formation of the five-component tip complex density, enhancing actin bundling ability. By studying a mutation of Gpsm2 associated with deafness, it provides insights into the importance of Gpsm2-G alpha i in specifying the tallest stereocilia.
Article
Biochemistry & Molecular Biology
Yong Liu, Lingxuan Li, Cong Yu, Fuxing Zeng, Fengfeng Niu, Zhiyi Wei
Summary: The study predicts the complex structures of Myo2-GTD and its cargo adaptors using ColabFold and summarizes the versatile cargo-recognition mechanisms of Myo2 by comparing the interaction details of multiple complexes. The research provides an efficient solution for studying protein-protein interactions.
Article
Biochemistry & Molecular Biology
Liping He, Wenli Jiang, Jianchao Li, Chao Wang
Summary: This study reveals the molecular basis of AnkG-Nfasc binding, defines the mechanisms of AnkG-Nfasc complex formation, and highlights the importance of AnkG-dependent clustering of Nfasc for AIS integrity.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Xuanyan Jia, Leishu Lin, Shun Xu, Lingxuan Li, Zhiyi Wei, Cong Yu, Fengfeng Niu
Summary: This study identified a specific binding interaction between the SH3 domain of ASAP1 and the PRM domain of MICAL1, and revealed the unique structure of the target-binding pocket in ASAP1-SH3. This unique structure was also found in the SH3 domains of GRAF and SKAP1. Furthermore, over 130 proteins with the SH3(AGS)-binding PRM were found in the protein database. Gene ontology analysis suggests that the strong interaction between SH3(AGS)-containing proteins and their targets may play roles in actin cytoskeleton regulation and vesicle trafficking.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Gaowei Jin, Leishu Lin, Kaiyue Li, Jiashan Li, Cong Yu, Zhiyi Wei
Summary: ELKS proteins play a crucial role in intracellular vesicle trafficking and targeting. This study elucidated the molecular mechanism of ELKS1 recognizing Rab6B and the impact of liquid-liquid phase separation (LLPS) on the interaction between ELKS1 and Rab6B. The findings suggest that ELKS1 facilitates vesicle release through its interaction with Rab6. These findings provide important insights into the spatiotemporal regulation of vesicle trafficking.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2023)
Article
Multidisciplinary Sciences
Amit Kumar Gaurav, Marjia Afrin, Xian Yang, Arpita Saha, S. K. Abdus Sayeed, Xuehua Pan, Zeyang Ji, Kam-Bo Wong, Mingjie Zhang, Yanxiang Zhao, Bibo Li
Summary: Trypanosoma brucei is a protozoan parasite that causes human African trypanosomiasis. TbRAP1, a telomere protein, has been shown to silence VSG genes by binding to dsDNA. However, the mechanism by which TbRAP1 allows the expression of a single active VSG gene was unknown. In this study, the researchers unexpectedly discovered an RNA Recognition Motif (RRM) in TbRAP1, which is unprecedented for RAP1 homologs. They found that TbRAP1 RRM, assisted by a specific patch, can recognize and bind to the 3'UTR sequences of VSG genes. Mutating the conserved residues in RRM abolished RNA binding activity, significantly decreased the level of active VSG RNA, and derepressed silent VSG genes. Their findings suggest a monoallelic expression mechanism for VSG genes, in which the abundant RNA of the active VSG gene antagonizes TbRAP1's silencing effect.
NATURE COMMUNICATIONS
(2023)
Article
Cell Biology
Qixu Cai, Xiumin Chen, Shihan Zhu, Roger A. Nicoll, Mingjie Zhang
Summary: Calcium calmodulin-dependent kinase II (CaMKII) is crucial for synaptic transmission and plasticity. The length of the unstructured linker between the kinase domain and the oligomerizing hub plays a crucial role in determining the ability of CaMKII to rescue defects in synaptic transmission and long-term potentiation. The phase separation capacity of CaMKII with GluN2B is critical for its cellular functions in the brain.
Article
Biology
Zeyu Shen, Bowen Jia, Yang Xu, Jonas Wessen, Tanmoy Pal, Hue Sun Chan, Shengwang Du, Mingjie Zhang, Rohit Pappu
Summary: Formation of membraneless organelles or biological condensates via phase separation expands the cellular organelle repertoire. In this study, an adaptive single-molecule imaging method was developed to track individual molecules in various biological condensates. The method enables measurements of concentrations, motion behavior, and molecular exchanges between condensed and dilute phases. The findings offer insights into the molecular mechanisms underlying the assembly and dynamics of biological condensates.
Article
Biology
Xudong Chen, Bowen Jia, Shihan Zhu, Mingjie Zhang
Summary: The volume and electric strength of an excitatory synapse are correlated with the area of its postsynaptic density (PSD). The molecular mechanism underlying the communication between the PSD assembly and spine actin cytoskeleton is poorly understood. This study discovers that PSD condensates can promote actin polymerization and bundling, and the Homer scaffold protein and a positively charged actin-binding surface of the Homer EVH1 domain are essential for this process. The communication between PSD and spine cytoskeleton may be modulated by targeting the phase separation of the PSD condensates.
Article
Multidisciplinary Sciences
Meng Zhang, Aili Cao, Lin Lin, Ying Chen, Yuan Shang, Chao Wang, Mingjie Zhang, Jinwei Zhu
Summary: The truncated guanylate kinase (GK) domain of MAGI2 interacts with its adjacent PDZ0 domain to form a supramodule capable of recognizing phosphoproteins. Identification of a phosphorylation-dependent binding motif for PDZ0-GK leads to the discovery of previously unknown binding partners. The structure and function of the MAGI2-target complex is explored using an inhibitory peptide derived from the consensus motif, revealing the action mechanism of cryptic MAGI GKs and broadening our understanding of target recognition rules of phosphoprotein binding modules.
Article
Biochemistry & Molecular Biology
Fa Zhang, Jiasheng Chen, Yahong Li, Jin Ye, Chao Wang, Volkmar Lessmann
Summary: The study reveals the molecular basis of the interaction between ARMS and Syt4, confirming the direct interaction between ARMS and Syt4 through their respective protein domains. Two essential residues, E15 and W72, of ARMS are identified as mediators of the formation of the complex.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)