Article
Cell Biology
Tanima Dutta, Harpreet Singh, Jason E. Gestwicki, Gregory L. Blatch
Summary: Plasmodium falciparum survival in the human host relies on its heat shock proteins and co-chaperone J domain proteins, which form chaperone-co-chaperone complexes. The exported PfJDP has been shown to stimulate the ATPase activity of PfHsp70-x and associate with other JDPs and Hsp70-x in mobile structures, providing valuable insights for future antimalarial drug discovery studies.
CELL STRESS & CHAPERONES
(2021)
Article
Cell Biology
Lena Eismann, Igor Fijalkowski, Carla Veronica Galmozzi, Jiri Koubek, Frank Tippmann, Petra Van Damme, Guenter Kramer
Summary: This study reveals the role of SecB chaperone protein in co-translational translocation, showing that SecB primarily interacts with inner membrane proteins (IMPs) and other nascent cytoplasmic and translocated proteins, regulated by the chaperone trigger factor. The findings suggest an important function of SecB in protein maturation.
Article
Biochemistry & Molecular Biology
Erin E. Deans, Judy L. M. Kotler, Wei-Shao Wei, Timothy O. Street
Summary: This study investigates the interaction between Hsp70 chaperones and client protein proIGF2, revealing that electrostatic attraction plays a crucial role in facilitating the recognition of oligomers.
JOURNAL OF MOLECULAR BIOLOGY
(2022)
Article
Multidisciplinary Sciences
Hiroki Tanemura, Kenji Masuda, Takeshi Okumura, Eri Takagi, Daisuke Kajihara, Hirofumi Kakihara, Koichi Nonaka, Ryo Ushioda
Summary: In this study, a novel high-expression promoter was cloned based on transcriptome analysis to significantly enhance mAb production in CHO cells. The promoter showed improved productivity for various IgG subclasses and may be a new method for maintaining protein homeostasis and achieving stable expression of introduced mAb genes.
SCIENTIFIC REPORTS
(2022)
Article
Biochemistry & Molecular Biology
Afrooz Dabbaghizadeh, Alexandre Pare, Zacharie Cheng-Boivin, Robin Dagher, Sandra Minotti, Marie-Josee Dicaire, Bernard Brais, Jason C. Young, Heather D. Durham, Benoit J. Gentil
Summary: Autosomal Recessive Spastic Ataxia of the Charlevoix Saguenay (ARSACS) is a genetic disease caused by mutation in the SACS gene, resulting in loss of function of the protein sacsin. The SacsJ domain of sacsin plays a key role in regulating the neurofilament (NF) and vimentin intermediate filament (IF) networks in cells.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Biochemistry & Molecular Biology
Shu-ou Shan
Summary: The Hsp70 family of molecular chaperones plays a central role in assisting the biogenesis of newly synthesized proteins. Apart from facilitating protein folding, Hsp70 also directs client proteins to specific biogenesis and quality control pathways. This paper presents accumulating evidence of a new branch in the Hsp70 network, involving the post-translational targeting of nascent membrane and organellar proteins. Via interactions with components of protein targeting and translocation machineries, Hsp70 initiates complex substrate relays to deliver nascent membrane proteins to the correct cellular membrane. The mechanistic principles of well-studied Hsp70-dependent targeting pathways are discussed, as well as observations and unanswered questions in less well-studied systems.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Shinya Sugimoto, Kunitoshi Yamanaka, Tatsuya Niwa, Yurika Terasawa, Yuki Kinjo, Yoshimitsu Mizunoe, Teru Ogura
Summary: This study demonstrated the role of JDPs in bacterial survival during heat stress and the formation of curli-extracellular amyloid fibers. Genetic analysis revealed the essential role of DnaJ in survival at high temperature and the ability of either DnaJ or CbpA to activate curli production. Biochemical analyses showed that DnaJ and CbpA are involved in regulating the master regulator CsgD and maintaining CsgA in a translocation-competent state.
JOURNAL OF MOLECULAR BIOLOGY
(2021)
Article
Biochemical Research Methods
Madison T. Wright, Logan Kouba, Lars Plate
Summary: Thyroglobulin (Tg) gene mutations lead to defects in Tg protein processing and secretion, often associated with abnormalities in protein homeostasis network interactions. Modulating dysregulated proteostasis components and pathways may serve as a therapeutic strategy to restore Tg secretion and thyroid hormone biosynthesis.
MOLECULAR & CELLULAR PROTEOMICS
(2021)
Article
Biochemistry & Molecular Biology
Alisa Mikhaylina, Natalia Lekontseva, Victor Marchenkov, Viktoria Kolesnikova, Albina Khairetdinova, Oleg Nikonov, Vitalii Balobanov
Summary: This study investigated the possibilities and limitations of using circular homo-oligomeric Sm-like proteins as a base for attaching other domains. A circular homoheptameric Sm-like protein from Sulfolobus acidocaldarius was chosen as a stable backbone, and the apical domain of the GroEL chaperone protein was attached. The engineered fusion protein exhibited similar binding and molecular chaperone activity as the full-length GroEL chaperone, demonstrating the effectiveness of this protein engineering approach for creating and stabilizing oligomeric proteins.
Review
Biochemistry & Molecular Biology
Da Been Kim, Changhee Na, Inhwan Hwang, Dong Wook Lee
Summary: Eukaryotic subcellular organelles are surrounded by lipid membranes. Vesicle trafficking is the primary mechanism for delivering organellar proteins in an endomembrane system. However, proteins translated in the cytosol are directly imported into their target organelles.
JOURNAL OF INTEGRATIVE PLANT BIOLOGY
(2023)
Article
Biochemical Research Methods
Kodai Machida, Shoma Miyawaki, Kuru Kanzawa, Taiki Hakushi, Tomonori Nakai, Hiroaki Imataka
Summary: The study successfully reconstituted human factors in a cell-free protein synthesis system, reproducing the biogenesis of beta-actin in a test tube, and providing a research tool for genetic mutations related to diseases.
ACS SYNTHETIC BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Hyunju Cho, Woo Jun Shim, Yumeng Liu, Shu-ou Shan
Summary: J-domain proteins (JDPs) play crucial roles in assisting Hsp70 in client trapping and regulating the Hsp70 ATPase cycle. In this study, it was found that two JDPs, Ydj1 and Sis1, work in parallel to support the targeting of tail-anchored proteins (TAs) to the endoplasmic reticulum (ER). Biochemical analyses showed that both Ydj1 and Sis1 enhance the transfer of Hsp70-bound TAs to Sgt2, ultimately supporting TA insertion in vivo.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Article
Microbiology
Linda C. Horianopoulos, Christopher W. J. Lee, Kerstin Schmitt, Oliver Valerius, Guanggan Hu, Melissa Caza, Gerhard H. Braus, James W. Kronstad
Summary: This study identifies a nuclear J domain protein, Dnj4, in the fungal pathogen Cryptococcus neoformans, demonstrating its role as a histone chaperone important for maintaining genome integrity and responding to DNA damage. Dnj4 regulates iron homeostasis and plays a crucial role in DNA damage response in C. neoformans. Additionally, Dnj4 functions as a conserved histone chaperone disrupting endogenous histone chaperoning machinery, suggesting its potential in understanding biological processes across different organisms.
Article
Biochemistry & Molecular Biology
Xinchen Lv, Xiaolin Zeng, Hongmiao Hu, Lixian Chen, Fan Zhang, Rui Liu, Yue Liu, Xuelin Zhou, Changshi Wang, Zhe Wu, Chanhong Kim, Yuehui He, Jiamu Du
Summary: Research shows that CONSTANS (CO) is a master transcription factor in triggering the floral transition in plants and is closely related to the regulation of the FLOWERING LOCUS T (FT) gene. CO binds to NUCLEAR FACTOR-YB/YC and forms a high affinity and specificity for the FT promoter through multivalent binding, regulating the transition of floral period.
Review
Biochemistry & Molecular Biology
Kalliopi Ziaka, Jacqueline van der Spuy
Summary: This review explores the role of Hsp90 in the proteostatic mechanisms of photoreceptors and elaborates on its function when retinal homeostasis is disturbed. It also discusses the impact of Hsp90 on retinal diseases through its interaction with specific client proteins.
Article
Cell Biology
Avi J. Samelson, Quang Dinh Tran, Remy Robinot, Lucia Carrau, Veronica V. Rezelj, Alice Mac Kain, Merissa Chen, Gokul N. Ramadoss, Xiaoyan Guo, Shion A. Lim, Irene Lui, James K. Nunez, Sarah J. Rockwood, Jianhui Wang, Na Liu, Jared Carlson-Stevermer, Jennifer Oki, Travis Maures, Kevin Holden, Jonathan S. Weissman, James A. Wells, Bruce R. Conklin, Benjamin R. TenOever, Lisa A. Chakrabarti, Marco Vignuzzi, Ruilin Tian, Martin Kampmann
Summary: The protein BRD2 is found to be crucial for ACE2 transcription and SARS-CoV-2 infection in human lung epithelial cells and cardiomyocytes. BRD2 inhibitors can effectively block endogenous ACE2 expression and viral infection in human cells, including nasal epithelial cells. Furthermore, inhibiting BRD2 with a drug called ABBV-744 can suppress SARS-CoV-2 replication in Syrian hamsters. BRD2 also controls the transcription of several other genes induced by SARS-CoV-2 infection, including the interferon response, which regulates the antiviral response.
NATURE CELL BIOLOGY
(2022)
Article
Multidisciplinary Sciences
Noa Dahan, Yury S. Bykov, Elizabeth A. Boydston, Amir Fadel, Zohar Gazi, Hodaya Hochberg-Laufer, James Martenson, Vlad Denic, Yaron Shav-Tal, Jonathan S. Weissman, Naama Aviram, Einat Zalckvar, Maya Schuldiner
Summary: This study discovered that translation of specific peroxisomal membrane proteins (PMPs) occurs on the surface of peroxisomes in yeast, similar to chloroplasts, mitochondria, and the endoplasmic reticulum. This localized translation process ensures the correct insertion of hydrophobic proteins into the peroxisomal membrane. Proper targeting of PMP transcripts to peroxisomes is crucial for cellular and peroxisomal function, highlighting the importance of localized translation in cellular physiology.
Article
Medicine, Research & Experimental
Aidan W. Porter, Diep N. Nguyen, Dennis R. Clayton, Wily G. Ruiz, Stephanie M. Mutchler, Evan C. Ray, Allison L. Marciszyn, Lubika J. Nkashama, Arohan R. Subramanya, Sebastien Gingras, Thomas R. Kleyman, Gerard Apodaca, Linda M. Hendershot, Jeffrey L. Brodsky, Teresa M. Buck
Summary: Molecular chaperones, such as GRP170, play a crucial role in maintaining cellular homeostasis and kidney physiology. Deficiency of GRP170 causes hypovolemia, hyperaldosteronemia, ion homeostasis dysregulation, loss of epithelial sodium channel (ENaC), and exhibits signs of acute kidney injury. Furthermore, GRP170 deficiency activates the unfolded protein response (UPR), which is also seen in various other causes of acute kidney injury.
Article
Biochemistry & Molecular Biology
Dian Yang, Matthew G. Jones, Santiago Naranjo, William M. Rideout III, Kyung Hoi (Joseph) Min, Raymond Ho, Wei Wu, Joseph M. Replogle, Jennifer L. Page, Jeffrey J. Quinn, Felix Horns, Xiaojie Qiu, Michael Z. Chen, William A. Freed-Pastor, Christopher S. McGinnis, David M. Patterson, Zev J. Gartner, Eric D. Chow, Trever G. Bivona, Michelle M. Chan, Nir Yosef, Tyler Jacks, Jonathan S. Weissman
Summary: Tumor evolution is driven by progressive genetic and epigenetic alterations, enabling unrestricted growth and expansion. This study provides insights into the hierarchical nature of tumor evolution through tracking phylogenetic relationships between cancer cells, allowing for in-depth studies of tumor progression.
Meeting Abstract
Biochemistry & Molecular Biology
Teresa M. Buck, Aidan Porter, Wily G. Ruiz, Dennis R. Clayton, Stephanie M. Mutchler, Evan C. Ray, Allison L. Marciszyn, Lubika J. NKashama, Arohan R. Subramanya, Sebastien Gingras, Thomas Kleyman, Gerard Apodaca, Linda M. Hendershot, Jeffrey L. Brodsky
Review
Biochemistry & Molecular Biology
R. Luke Wiseman, Jaleh S. Mesgarzadeh, Linda M. Hendershot
Summary: Cells adapt endoplasmic reticulum quality control (ERQC) to match the diverse demands encountered during normal physiology and in disease through the unfolded protein response (UPR), which plays a crucial role in maintaining ER function.
Article
Multidisciplinary Sciences
Nathan H. Cho, Keith C. Cheveralls, Andreas-David Brunner, Kibeom Kim, Andre C. Michaelis, Preethi Raghavan, Hirofumi Kobayashi, Laura Savy, Jason Y. Li, Hera Canaj, James Y. S. Kim, Edna M. Stewart, Christian Gnann, Frank McCarthy, Joana P. Cabrera, Rachel M. Brunetti, Bryant B. Chhun, Greg Dingle, Marco Y. Hein, Bo Huang, Shalin B. Mehta, Jonathan S. Weissman, Rafael Gomez-Sjoberg, Daniel N. Itzhak, Loic A. Royer, Matthias Mann, Manuel D. Leonetti
Summary: This article introduces a method that uses various techniques to systematically map the localization and interactions of human proteins, and discovers the rich functional information contained in protein localization patterns.
Review
Cell Biology
Bradley W. Wright, Zixin Yi, Jonathan S. Weissman, Jin Chen
Summary: Omics-based technologies have revealed the existence of unannotated open reading frames (ORFs) in genomes, which have the potential to encode novel functional proteins or have regulatory roles. However, there is still limited understanding of these noncanonical ORFs in the scientific community, despite the few that have been studied and shown to play important roles in biological processes.
TRENDS IN CELL BIOLOGY
(2022)
Article
Multidisciplinary Sciences
Kristine F. R. Pobre-Piza, Melissa J. Mann, Ashley R. Flory, Linda M. Hendershot
Summary: The co-chaperones BiP, ERdj4, ERdj5, and GRP170 associate with aggregation-prone peptides. In this study, the impact of Interstitial Lung Disease (ILD)-associated mutants of surfactant protein C (SP-C) on protein maturation is investigated. The authors demonstrate that the ILD mutants disrupt di-sulfide bond formation and expose aggregation-prone peptides, leading to binding with ERdj4, ERdj5, and GRP170. Furthermore, the destabilized mutant BRICHOS domain affects the insertion of its transmembrane (TM) region in the ER membrane. This study provides insights into chaperone specificity, the recognition of aggregation-prone regions, and the consequences of disease-associated mutants on protein folding.
NATURE COMMUNICATIONS
(2022)
Article
Multidisciplinary Sciences
Rachael K. Wood, Ashley R. Flory, Melissa J. Mann, Lindsay J. Talbot, Linda M. Hendershot
Summary: Pechatric osteosarcomas (OS) display a dilated endoplasmic reticulum (ER) due to reduced expression of COPII vesicle components, leading to abnormal accumulation of procollagen-I protein. Restoring the expression of two specific components resolves the ER morphology and enhances protein secretion, without affecting orthotopic xenograft growth.
Article
Biochemistry & Molecular Biology
Joseph M. Replogle, Reuben A. Saunders, Angela N. Pogson, Jeffrey A. Hussmann, Alexander Lenail, Alina Guna, Lauren Mascibroda, Eric J. Wagner, Karen Adelman, Gila Lithwick-Yanai, Nika Iremadze, Florian Oberstrass, Doron Lipson, Jessica L. Bonnar, Marco Jost, Thomas M. Norman, Jonathan S. Weissman
Summary: Understanding the relationships between genotypes and phenotypes is a central goal in genetics. This study demonstrates the use of a high-content phenotypic screening technique, Perturb-seq, to analyze over 2.5 million human cells at a genome-wide scale. Through this analysis, new gene functions and complex cellular phenomena were revealed.
Article
Biotechnology & Applied Microbiology
Fulong Yu, Liam D. Cato, Chen Weng, L. Alexander Liggett, Soyoung Jeon, Keren Xu, Charleston W. K. Chiang, Joseph L. Wiemels, Jonathan S. Weissman, Adam J. de Smith, Vijay G. Sankaran
Summary: Genome-wide association studies combined with single-cell genomic atlases can reveal the mechanisms of disease-causal genetic variations. However, sparse and noisy single-cell epigenomic data analysis often hinders the identification of disease-relevant cell types. To overcome this, the SCAVENGE algorithm uses network propagation to map causal variants to their relevant cellular context at a single-cell resolution, successfully identifying key biological mechanisms in various blood traits and diseases.
NATURE BIOTECHNOLOGY
(2022)
Article
Cell Biology
Melissa J. Mann, Ashley R. Flory, Christina Oikonomou, Candace A. Hayes, Chris Melendez-Suchi, Linda M. Hendershot
Summary: This study identifies two rate-limiting steps in the degradation of non-secreted antibodies and explains the details and functions of these steps.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Editorial Material
Cell Biology
Silvia Masciarelli, Francesco Fazi, Linda M. Hendershot
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2023)
Article
Multidisciplinary Sciences
Christoph Bock, Paul Datlinger, Florence Chardon, Matthew A. Coelho, Matthew B. Dong, Keith A. Lawson, Tian Lu, Laetitia Maroc, Thomas M. Norman, Bicna Song, Geoff Stanley, Sidi Chen, Mathew Garnett, Wei Li, Jason Moffat, Lei S. Qi, Rebecca S. Shapiro, Jay Shendure, Jonathan S. Weissman, Xiaowei Zhuang
Summary: CRISPR screens are a powerful tool for unbiased investigation of gene functions in various applications and species. By introducing genetically encoded perturbations into cell pools, these screens allow the evaluation of gene effects under biological challenges. High-content read-outs and dedicated software tools enhance the analysis and reproducibility of the results, making it a flexible and reliable method for biological discovery and drug development.
NATURE REVIEWS METHODS PRIMERS
(2022)