Article
Biochemistry & Molecular Biology
Ana G. Pedrosa, Tania Francisco, Tony A. Rodrigues, Maria J. Ferreira, Gerbrand J. van der Heden van Noort, Jorge E. Azevedo
Summary: The study investigated the extraction mechanism of PEX5 using a cell-free in vitro system and various engineered molecules. It was found that ubiquitinated PEX5 can be extracted, and the N- and C-terminus of PEX5 are not crucial for the extraction process. The study also revealed that the PEX5-linked monoubiquitin is unfolded prior to extraction, and intramolecularly cross-linked ubiquitin at residue 11 of PEX5 inhibits extraction.
JOURNAL OF MOLECULAR BIOLOGY
(2023)
Article
Cell Biology
Xiaoman You, Shanshan Zhu, Haowen Sheng, Zheng Liu, Dan Wang, Min Wang, Xiao Xu, Feng He, Hong Fang, Fan Zhang, Debao Wang, Zeyun Hao, Ruyi Wang, Yinghui Xiao, Jianmin Wan, Guo-Liang Wang, Yuese Ning
Summary: Knockdown of OsPEX5 enhances resistance to rice blast fungus Magnaporthe oryzae. OsPEX5 interacts with E3 ubiquitin ligase APIP6 to regulate plant immunity. Additionally, OsPEX5 interacts with OsALDH2B1 to enhance its repression of defense gene expression.
Article
Multidisciplinary Sciences
Valeria Napolitano, Charlotte A. Softley, Artur Blat, Vishal C. Kalel, Kenji Schorpp, Till Siebenmorgen, Kamyar Hadian, Ralf Erdmann, Michael Sattler, Grzegorz M. Popowicz, Grzegorz Dubin
Summary: Trypanosomiasis is a life-threatening infection and requires new therapeutic approaches. In this study, the researchers identified the PEX5-PTS1 interaction as a key player in the import of glycolytic enzymes in Trypanosoma. They developed a fluorescence polarization-based method and successfully identified small molecule inhibitors that can disrupt this interaction and inhibit parasite growth in cell culture.
SCIENTIFIC REPORTS
(2022)
Article
Cell Biology
Stefan Gaussmann, Mohanraj Gopalswamy, Maike Eberhardt, Maren Reuter, Peijian Zou, Wolfgang Schliebs, Ralf Erdmann, Michael Sattler
Summary: In this study, the membrane interactions of PEX5 and PEX14 NTDs were characterized in vitro using membrane mimicking bicelles and nanodiscs, revealing weak interaction of PEX14 NTD with bicelles and multiple interaction sites of PEX5 NTD involving amphipathic alpha-helical regions. Interestingly, the interaction between PEX5 and PEX14 NTDs was found to be largely unaffected by the presence of the membrane, suggesting that docking of PEX5 to PEX14 at the membrane does not reduce the overall binding affinity between the two proteins in the assembly of the peroxisome translocon.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Multidisciplinary Sciences
Peiqiang Feng, Xudong Wu, Satchal K. Erramilli, Joao A. Paulo, Pawel Knejski, Steven P. Gygi, Anthony A. Kossiakoff, Tom A. Rapoport
Summary: Peroxisomes are essential organelles for human health and the ligase complex plays a crucial role in the recycling of peroxisomal import receptors. The cryo-electron microscopy structure of the complex reveals its function as a retrotranslocation channel, clarifying an important step in peroxisomal protein import.
Article
Biochemistry & Molecular Biology
Amr Kataya, Sierra Mitchell, Rasha Etman, Marcus Samuel, Greg B. Moorhead
Summary: Protein phosphatase 2A (PP2A) is targeted to the plant peroxisome via a C-terminal SSL sequence on its regulatory B' theta (theta) subunit. The substrates of peroxisomal PP2A are unknown but are recruited by the regulatory B'theta subunit. Arabidopsis E3 ligase SINA-like 10 was identified as a B'theta binding partner, and it interacts with PP2A through the B'-binding SLiM motif. This interaction occurs in the cytosol and SINA-like 10 is then transported into peroxisomes.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2023)
Article
Microbiology
Kelong Ma, Rundong Shu, Hongtao Liu, Jiaqi Fu, Zhao-Qing Luo, Jiazhang Qiu
Summary: Legionella pneumophila, a pathogenic bacteria, can create an environment conducive to its replication by exploiting host cell signaling pathways and the ubiquitin system. In this study, we identified a novel effector protein, Lug15, which functions as an E3 ligase and remodels the Legionella phagosome.
Article
Multidisciplinary Sciences
Man Pan, Qingyun Zheng, Tian Wang, Lujun Liang, Junxiong Mao, Chong Zuo, Ruichao Ding, Huasong Ai, Yuan Xie, Dong Si, Yuanyuan Yu, Lei Liu, Minglei Zhao
Summary: This study reveals the mechanism of the N-degron pathway mediated by Ubr1, including key structural elements involved in the initiation and elongation steps of ubiquitination.
Article
Cell Biology
Elisabeth Rackles, Michael Witting, Ignasi Forne, Xing Zhang, Judith Zacherl, Simon Schrott, Christian Fischer, Jonathan J. Ewbank, Christof Osman, Axel Imhof, Stephane G. Rolland
Summary: Research shows the existence of organelle-specific retrograde signaling for peroxisomes, which plays an important role in responding to stress and infection, regulating lipid metabolism, immunity, and potentially acting as a protective mechanism.
Article
Biochemistry & Molecular Biology
Gurusamy Hariharasudhan, Seo-Yeon Jeong, Min-Ji Kim, Sung Mi Jung, Gwanwoo Seo, Ju-Ran Moon, Sumi Lee, In-Youb Chang, Younghoon Kee, Ho Jin You, Jung-Hee Lee
Summary: SUMOylation of RAD51 is crucial for its recruitment to chromatin and HR repair. TOPORS-mediated RAD51 SUMOylation plays a key role in promoting HR repair and genomic maintenance.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Chemistry, Medicinal
Gaoqi Weng, Dan Li, Yu Kang, Tingjun Hou
Summary: Proteolysis-targeting chimeras (PROTACs) represent an emerging drug discovery technology that selectively induce targeted protein degradation. PROTAC-Model, an integrative computational method, was developed to predict PROTAC-mediated ternary complex structures and showed better performance in rational design of PROTACs.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Medicinal
Valeria Napolitano, Piotr Mroz, Monika Marciniak, Vishal C. Kalel, Charlotte A. Softley, Julian D. Janna Olmos, Bettina G. Tippler, Kenji Schorpp, Sarah Rioton, Tony Froehlich, Oliver Plettenburg, Kamyar Hadian, Ralf Erdmann, Michael Sattler, Grzegorz M. Popowicz, Maciej Dawidowski, Grzegorz Dubin
Summary: Trypanosomiases are neglected tropical diseases caused by Trypanosoma (sub)species. The inhibition of the PEX5-PEX14 protein-protein interaction has shown potential as a lethal treatment for Trypanosoma. Researchers have developed a novel compound scaffold that inhibits PEX5-PEX14 PPI and has demonstrated trypanocidal activity in cell-based assays.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Multidisciplinary Sciences
Maximilian Ruettermann, Michelle Koci, Pascal Lill, Ermis Dionysios Geladas, Farnusch Kaschani, Bjoern Udo Klink, Ralf Erdmann, Christos Gatsogiannis
Summary: This study provides cryo-EM structures of Pex1/Pex6 and reveals their mechanism of protein substrate translocation. Pex1/Pex6 generates mechanical forces through ATP hydrolysis to drive substrate transport across the peroxisomal membrane.
NATURE COMMUNICATIONS
(2023)
Article
Biochemistry & Molecular Biology
Yulemi Gonzalez Quesada, Luc DesGroseillers
Summary: This study investigates the degradation mechanism of RNA-binding protein STAU1 in cancer cells. The research reveals that STAU1 degradation is related to the FPL-motif protein family and inflammation-related protein MAP4K1. Through experiments, it is confirmed that TRIM25 is the E3 ubiquitin ligase responsible for the degradation of STAU1 and MAP4K1. These findings are significant for further exploration of the inflammation mechanisms associated with cancer.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Cell Biology
Yotam David, Ines Gomes Castro, Eden Yifrach, Chen Bibi, Enas Katawi, Dekel Yahav Har-Shai, Sagie Brodsky, Naama Barkai, Tommer Ravid, Miriam Eisenstein, Shmuel Pietrokovski, Maya Schuldiner, Einat Zalckvar
Summary: Peroxisomes are essential for human health and survival as they host important metabolic enzymes. By using a high-throughput screen in yeast, researchers discovered 18 previously unidentified peroxisomal proteins and investigated their dependence on metabolic and targeting factors for peroxisomal localization. One newly identified protein, Pls1, was found to affect the lysine biosynthesis pathway.
Article
Microbiology
Guo-Yan Zhao, Li-Ya Zhao, Zhi-Jie Xia, Jin-Lei Zhu, Di Liu, Chun-Yue Liu, Xiu-Lan Chen, Yu-Zhong Zhang, Xi-Ying Zhang, Mei-Xue Dai
INTERNATIONAL JOURNAL OF SYSTEMATIC AND EVOLUTIONARY MICROBIOLOGY
(2017)
Article
Biochemistry & Molecular Biology
Gaurav Agrawal, Helen H. Shang, Zhi-Jie Xia, Suresh Subramani
JOURNAL OF BIOLOGICAL CHEMISTRY
(2017)
Article
Multidisciplinary Sciences
Wei Wang, Honghong Zhang, Sali Liu, Chung Kwon Kim, Yilin Xu, Lisa A. Hurley, Ryo Nishikawa, Motoo Nagane, Bo Hu, Alexander H. Stegh, Shi-Yuan Cheng, Chonghui Cheng
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2017)
Article
Cell Biology
Wei Wang, Zhijie Xia, Jean-Claude Farre, Suresh Subramani
Article
Genetics & Heredity
Carlos R. Ferreira, Zhi-Jie Xia, Aurelie Clement, David A. Parry, Mariska Davids, Fulya Taylan, Prashant Sharma, Coleman T. Turgeon, Bernardo Blanco-Sanchez, Bobby G. Ng, Clare V. Logan, Lynne A. Wolfe, Benjamin D. Solomon, Megan T. Cho, Ganka Douglas, Daniel R. Carvalho, Heiko Bratke, Marte Gjol Haug, Jennifer B. Phillips, Jeremy Wegner, Michael Tiemeyer, Kazuhiro Aoki, Ann Nordgren, Anna Hammarsjo, Angela L. Duker, Luis Rohena, Hanne Buciek Hove, Jakob Ek, David Adams, Cynthia J. Tifft, Tito Onyekweli, Tara Weixel, Ellen Macnamara, Kelly Radtke, Zoe Powis, Dawn Earl, Melissa Gabriel, Alvaro H. Serrano Russi, Lauren Brick, Mariya Kozenko, Emma Tham, Kimiyo M. Raymond, John A. Phillips, George E. Tiller, William G. Wilson, Rizwan Hamid, May C. V. Malicdan, Gen Nishimura, Giedre Grigelioniene, Andrew Jackson, Monte Westerfield, Michael B. Bober, William A. Gahl, Hudson H. Freeze
AMERICAN JOURNAL OF HUMAN GENETICS
(2018)
Article
Cell Biology
Xiaofeng Wang, Pingping Wang, Zhuangzhuang Zhang, Jean-Claude Farre, Xuezhi Li, Ruonan Wang, Zhijie Xia, Suresh Subramani, Changle Ma
Article
Genetics & Heredity
Carlos R. Ferreira, Wadih M. Zein, Laryssa A. Huryn, Andrea Merker, Seth I. Berger, William G. Wilson, George E. Tiller, Lynne A. Wolfe, Melissa Merideth, Daniel R. Carvalho, Angela L. Duker, Heiko Bratke, Marte Gjol Haug, Luis Rohena, Hanne B. Hove, Zhi-Jie Xia, Bobby G. Ng, Hudson H. Freeze, Melissa Gabriel, Alvaro H. Serrano Russi, Lauren Brick, Mariya Kozenko, Dawn L. Earl, Emma Tham, Gen Nishimura, John A. Phillips, William A. Gahl, Rizwan Hamid, Andrew P. Jackson, Giedre Grigelioniene, Michael B. Bober
GENETICS IN MEDICINE
(2020)
Article
Genetics & Heredity
Bobby G. Ng, Paulina Sosicka, Francois Fenaille, Annie Harroche, Sandrine Vuillaumier-Barrot, Mindy Porterfield, Zhi-Jie Xia, Shannon Wagner, Michael J. Bamshad, Marie-Christine Vergnes-Boiteux, Sophie Cholet, Stephen Dalton, Anne Dell, Thierry Dupre, Mathieu Fiore, Stuart M. Haslam, Yohann Huguenin, Tadahiro Kumagai, Michael Kulik, Katherine McGoogan, Caroline Michot, Deborah A. Nickerson, Tiffany Pascreau, Delphine Borgel, Kimiyo Raymond, Deepti Warad, Heather Flanagan-Steet, Richard Steet, Michael Tiemeyer, Nathalie Seta, Arnaud Bruneel, Hudson H. Freeze
Summary: The study identified a recurrent mutation in SLC37A4 causing a dominantly inherited congenital disorder of glycosylation characterized by coagulopathy and liver dysfunction with abnormal serum N-glycans. Liver-specific abnormalities in glycosylation were replicated in a CRISPR base-edited hepatoma cell line carrying the mutation. The mutant protein showed relocation to a non-Golgi compartment and altered Golgi morphology and reduced intraluminal pH, potentially explaining the glycosylation alterations.
AMERICAN JOURNAL OF HUMAN GENETICS
(2021)
Article
Oncology
Wei Huang, Jing Li, Hongtao Zhu, Xuhui Qin, Chao Chen, Bing Wang, Jinxia Wei, Yanyang Song, Xia Lu, Zhongyu Li, Wenqing Xia, Aodi He, Lidong Cheng, Xingjiang Yu, Kai Shu, Wei Wang
Summary: A novel EGFR variant (EGFRx) specifically expressed in GSCs was identified, which plays essential roles in maintaining the GSC phenotype and promoting GBM progression through constitutive activation of STAT5. This finding suggests that EGFRx-STAT5 signaling could be a promising therapeutic target for GBM.
Review
Cell Biology
Wei Wang, Suresh Subramani
Meeting Abstract
Biochemistry & Molecular Biology
Bobby G. Ng, Zhi-Jie Xia, David Scott, Hudson H. Freeze