Article
Multidisciplinary Sciences
Paula Rofes, Marta Pineda, Lidia Feliubadalo, Mireia Menendez, Rafael de Cid, Carolina Gomez, Eva Montes, Gabriel Capella, Joan Brunet, Jesus del Valle, Conxi Lazaro
Summary: This study validated that the shorter transcript produced by the BARD1 c.1977A>G variant is a constitutive splicing product rather than an aberrant transcript. Following ACMG/AMP guidelines, this variant should be considered as likely benign.
SCIENTIFIC REPORTS
(2021)
Article
Biochemistry & Molecular Biology
Hosub Park, Hwangkyu Son, Hyebin Cha, Kihyuk Song, Seongsik Bang, Seungyun Jee, Hyunsung Kim, Jaekyung Myung, Su-Jin Shin, Chihwan Cha, Min Sung Chung, Seungsam Paik
Summary: This study found that low ASAP1 expression was associated with worse recurrence-free survival in invasive breast cancer, particularly in ER-positive cases.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Broto Chakrabarty, Nita Parekh
Summary: This study classifies and analyzes human ANKYRIN proteins to understand their diversity and their significance in disease association.
Article
Multidisciplinary Sciences
Christoph Heintze, Iaroslav Babenko, Jirina Zackova Suchanova, Alastair Skeffington, Benjamin M. Friedrich, Nils Kroeger
Summary: Biomineral-forming organisms produce inorganic materials with complex morphologies. This study focused on diatoms and identified new biomineralization proteins involved in silica biosynthesis. Knocking out specific genes led to aberrations in silica biogenesis, suggesting a mechanism of liquid-liquid phase separation for pore pattern morphogenesis.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Multidisciplinary Sciences
Katrin Stuber, Tobias Schneider, Jill Werner, Michael Kovermann, Andreas Marx, Martin Scheffner
Summary: The study reveals that NEDD8 can be phosphorylated at S65, affecting its structural dynamics similar to Ub. Phosphorylated NEDD8 has a distinct interactome compared to unmodified Ub and NEDD8, and it can more effectively regulate HSP70 protein activity.
NATURE COMMUNICATIONS
(2021)
Article
Chemistry, Medicinal
Lin Niu, Yu-jie Lu, Xing-wang Zu, Wen Yang, Fu-kui Shen, Yan-yan Xu, Min Jiang, Yang Xie, Su-yun Li, Jie Gao, Gang Bai
Summary: This study focuses on the role of TRPV4 in fibrosis in chronic obstructive pulmonary disease (COPD) and investigates the therapeutic effect and mechanism of action of magnolol (MAG) on TRPV4. The results demonstrate that MAG disrupts the binding between phosphatidylinositol 3 kinase and TRPV4 by targeting its ankyrin repeat domain (ARD), inhibiting the membrane distribution and channel activity of TRPV4, consequently alleviating fibrosis in COPD.
PHYTOTHERAPY RESEARCH
(2023)
Article
Multidisciplinary Sciences
Qi Hu, Maria Victoria Botuyan, Debiao Zhao, Gaofeng Cui, Elie Mer, Georges Mer
Summary: The BRCA1-BARD1 tumor suppressor complex plays a crucial role in DNA repair through homologous recombination. The complex is recruited to damaged chromatin and catalyzes ubiquitylation of histones, with BARD1's ankyrin repeat and BRCT domains binding to nucleosomal histones, DNA, and monoubiquitin attached to H2A. This mechanism involves a regulatory crosstalk between BRCA1-BARD1 and H2A, promoting ubiquitylation and opposing 53BP1 to promote homologous recombination.
Article
Biochemistry & Molecular Biology
Sebastian Kostrhon, J. Rajan Prabu, Kheewoong Baek, Daniel Horn-Ghetko, Susanne von Gronau, Maren Kluegel, Jerome Basquin, Arno F. Alpi, Brenda A. Schulman
Summary: The study investigates the cooperation of two distinct E3 ligases, revealing the role of ARIH2 in the ubiquitylation of substrates of neddylated CUL5-RBX2-based E3s. It is found that NEDD8 regulates cullin-specifically by recruiting ARIH family members through allosteric mechanism. Through structural analyses, it is shown how a ubiquitin-like protein induces protein-protein interactions indirectly, offering potential therapeutic targeting opportunities.
NATURE CHEMICAL BIOLOGY
(2021)
Article
Cell Biology
Thaddaeus Mutugi Nthiga, Birendra Kumar Shrestha, Jack-Ansgar Bruun, Kenneth Bowitz Larsen, Trond Lamark, Terje Johansen
Summary: The Golgi complex plays a crucial role in the processing and trafficking of proteins and lipids, with its turnover regulated to meet cellular demands. This study uncovers a mechanism where CALCOCO1 interacts with ZDHHC17 to facilitate Golgi degradation through autophagy, influencing Golgi size and morphology during starvation.
JOURNAL OF CELL BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Linchang Dai, Yaxin Dai, Jinhua Han, Yan Huang, Longge Wang, Jun Huang, Zheng Zhou
Summary: The study reveals the mechanism of BRCA1-BARD1 complex recruitment and retention by DSB-flanking nucleosomes, shedding light on cancer therapeutic avenues.
Article
Biochemistry & Molecular Biology
Liam Butler, Carolina Locatelli, Despoina Allagioti, Irina Lousa, Kimon Lemonidis, Nicholas C. O. Tomkinson, Christine Salaun, Luke H. Chamberlain
Summary: S-acylation is an important post-translational modification mediated by the zDHHC enzyme family. This study focused on the S-acylation of Sprouty and SPRED proteins by zDHHC17. Surprisingly, the zDHHC ANK binding motif (zDABM) was found to be dispensable for S-acylation in Sprouty-2, and SPRED3, which lacks zDABM, was efficiently S-acylated. Mutational analysis revealed that the cysteine-rich SPR domain of SPRED3 interacts with zDHHC17, independent of ANK17. Thus, zDHHC17 can recognize its substrates through both zDABM-dependent and zDABM-independent mechanisms.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Burak T. Kaynak, Zakaria L. Dahmani, Pemra Doruker, Anupam Banerjee, Shang-Hua Yang, Reuven Gordon, Laura S. Itzhaki, Ivet Bahar
Summary: PR65, a scaffold composed of 15 HEAT repeats, forms the heterotrimeric protein phosphatase PP2A with catalytic and regulatory subunits. Our study reveals the flexibility of PR65 allows for distance fluctuations and its dynamics facilitate complexation with the catalytic subunit, providing the mechanical framework for enzymatic activity. The coils at the C-terminal arm of PR65 play an important role in mediating the collective dynamics of PP2A, suggesting potential target sites for modulating PR65 function.
Article
Biochemistry & Molecular Biology
Jiawen Zhao, Yongxian Wu, Kai Zhou, Moran Huang, Yan Sun, Juening Kang, Qisheng Su, Yutong Zhao, Quan Liu, Chengyang Li
Summary: The study aimed to investigate the role of ferroptosis in the formation of calcium oxalate kidney stones and the regulation mechanism of the ANKRD1 gene. The Nrf2/HO-1 and p53/SLC7A11 signaling pathways were found to be activated in the kidney stone model group, leading to reduced expression of ferroptosis marker proteins and increased expression of iron transport-related proteins. The silencing or overexpression of ANKRD1 regulated the p53/SLC7A11 signaling pathway and ferroptosis induced by calcium oxalate crystals. Overall, calcium oxalate crystals can mediate ferroptosis and ANKRD1 participates in the formation and development of calcium oxalate kidney stones.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
(2023)
Review
Biochemistry & Molecular Biology
Annalisa L. E. Carli, Joshua M. Hardy, Hanadi Hoblos, Matthias Ernst, Isabelle S. Lucet, Michael Buchert
Summary: This review examines the functions of DCLK1 and predicts the effects of somatic missense mutations on its functions. DCLK1 is a microtubule-associated protein that plays a role in cancer development. Mutations in DCLK1 primarily affect its binding and stability with microtubules, leading to altered microtubule dynamics.
Editorial Material
Multidisciplinary Sciences
Jochen Balbach, Milton T. Stubbs
Summary: Phage protein E kills bacteria by shutting down cell wall biosynthesis.
Article
Biochemistry & Molecular Biology
Samuel R. Witus, Anika L. Burrell, Daniel P. Farrell, Jianming Kang, Meiling Wang, Jesse M. Hansen, Alex Pravat, Lisa M. Tuttle, Mikaela D. Stewart, Peter S. Brzovic, Champak Chatterjee, Weixing Zhao, Frank DiMaio, Justin M. Kollman, Rachel E. Klevit
Summary: Mutations in the RING domains of the E3 ubiquitin ligase BRCA1/BARD1 increase the risk of breast and ovarian cancers. The structure of the BRCA1/BARD1 RING heterodimer with UbcH5c bound to the nucleosome, along with biochemical data, explains how the complex selectively ubiquitylates specific lysines in H2A. The findings provide insight into how E3 ligases target lysine residues in nucleosomes and how mutations in cancer patients affect this process.
NATURE STRUCTURAL & MOLECULAR BIOLOGY
(2021)
Article
Microbiology
Dagmara Kisiela, Pearl Magala, Gianluca Interlandi, Laura A. Carlucci, Angelo Ramos, Veronika Tchesnokova, Benjamin Basanta, Vladimir Yarov-Yarovoy, Hovhannes Avagyan, Anahit Hovhannisyan, Wendy E. Thomas, Ronald E. Stenkamp, Rachel E. Klevit, Evgeni Sokurenko
Summary: The study identified a novel antibody that acts as a kinetic trap to prevent the conformational transitions of FimH protein, leading to a significant slowing down of its ability to bind mannose and blocking bacterial adhesion. Residues Leu-34 and Val-35 of FimH were found to act as molecular toggle switches, which, when disrupted, hinder the conformational transition and adhesive function of the protein. The research also demonstrated that the allosteric switches are conserved across a diverse family of bacterial fimbrial adhesins.
Biographical-Item
Multidisciplinary Sciences
John D. Scott, Trisha N. Davis, Rachel E. Klevit, William A. Catterall
Review
Biochemistry & Molecular Biology
Samuel R. Witus, Weixing Zhao, Peter S. Brzovic, Rachel E. Klevit
Summary: Mutations in BRCA1 and BARD1 predispose carriers to breast and ovarian cancers. Recent advancements in structural and cellular biology have provided critical insights into how BRCA1/BARD1 serves as a nucleosome reader and writer, facilitating transcriptional regulation and DNA repair.
TRENDS IN BIOCHEMICAL SCIENCES
(2022)
Review
Biochemistry & Molecular Biology
Evgeni Sokurenko, Veronika Tchesnokova, Gianluca Interlandi, Rachel Klevit, Wendy E. Thomas
Summary: This article summarizes studies on various functional types of monoclonal antibodies obtained against different allosteric conformers of the mannose-specific bacterial adhesin FimH. Understanding the molecular mechanism of antibody action against allosteric proteins provides insights on how to design antibodies with desired functional effects, including those with neutralizing activity against bacterial and viral cell attachment proteins.
JOURNAL OF MOLECULAR BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Katherine H. Reiter, Alex Zelter, Maria K. Janowska, Michael Riffle, Nicholas Shulman, Brendan X. MacLean, Kaipo Tamura, Matthew C. Chambers, Michael J. MacCoss, Trisha N. Davis, Miklos Guttman, Peter S. Brzovic, Rachel E. Klevit
Summary: This study characterized the interaction between the auto-inhibited RBR ligase HHARI and its substrate 4EHP using a combination of techniques. The results revealed a binding platform on the catalytic domain of HHARI and the role of a phosphomimetic mutation in promoting the release and reorientation of Rcat for substrate modification. These findings identify a direct binding interaction between an RBR ligase and its substrate and propose a general model for substrate recognition.
Article
Biology
Atanas Radkov, Anne L. Sapiro, Sebastian Flores, Corey Henderson, Hayden Saunders, Rachel Kim, Steven Massa, Samuel Thompson, Chase Mateusiak, Jacob Biboy, Ziyi Zhao, Lea M. Starita, William L. Hatleberg, Waldemar Vollmer, Alistair B. Russell, Jean-Pierre Simorre, Spencer Anthony-Cahill, Peter Brzovic, Beth Hayes, Seemay Chou
Summary: Members of the T6SS amidase effector superfamily of toxins exhibit distinct antimicrobial potency across different competitor species. A study on Tae1 from Pseudomonas aeruginosa PAO1 using nuclear magnetic resonance and deep mutational scanning (DMS) revealed a distributed three-dimensional interaction interface with the cell wall network, providing an explanation for observed differences in antimicrobial potency across divergent Gram-negative competitors.
Article
Biology
Eugene Serebryany, Sourav Chowdhury, Christopher N. Woods, David C. Thorn, Nicki E. Watson, Arthur A. McClelland, Rachel E. Klevit, Eugene Shakhnovich
Summary: Cataract, a protein aggregation disorder, is a common cause of vision loss worldwide. Researchers have discovered that myo-inositol, an abundant lens metabolite, can suppress the aggregation of lens crystallins, suggesting it as a potential strategy to prevent or delay age-onset cataracts.
Article
Biochemistry & Molecular Biology
Ishor Thapa, Russell Vahrenkamp, Samuel R. Witus, Caitlin Lightle, Owen Falkenberg, Marlo K. Sellin Jeffries, Rachel E. Klevit, Mikaela D. Stewart
Summary: The tumor-suppressor proteins BRCA1 and BARD1 play important roles in transcriptional repression and DNA damage repair, and their functions are mediated through mono-ubiquitylation of histone H2A in nucleosomes. The study in C. elegans reveals that the orthologs BRC-1 and BRD-1 retain many functions of their human counterparts, including enzymatic activity toward nucleosomes. Despite differences in binding modes, BRC-1 and BRD-1 also contribute to gene repression in C. elegans. This highlights the conservation of these functions and allows further investigation using this model organism.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Samuel R. Witus, Lisa M. Tuttle, Wenjing Li, Alex Zelter, Meiling Wang, Klaiten E. Kermoade, Damien B. Wilburn, Trisha N. Davis, Peter S. Brzovic, Weixing Zhao, Rachel E. Klevit
Summary: BRCA1/BARD1 is a tumor suppressor gene with functions in DNA damage repair and transcriptional regulation. It interacts with nucleosomes and facilitates ubiquitylation of histone H2A. Our study reveals novel interactions involving an intrinsically disordered DNA-binding region of BARD1 that support H2A ubiquitylation and recruitment to chromatin and DNA damage sites. These interactions contribute to cell survival and identify a network of BARD1-nucleosome interactions on chromatin.
Meeting Abstract
Biophysics
Rachel Klevit, Amanda F. Clouser, Hannah E. E. R. Baughman, Chris Woods, Maria Janowska, Natalie Stone, Lindsey Ulmer, Matt Bush, Miklos Guttman
BIOPHYSICAL JOURNAL
(2022)
Meeting Abstract
Biochemistry & Molecular Biology
Russell Vahrenkamp, Sam Witus, Rachel Klevit, Mikaela Stewart
