Article
Biochemistry & Molecular Biology
Louise Laursen, Stefano Gianni, Per Jemth
Summary: This study investigates the folding of a three-domain supramodule from the protein PSD-95, revealing that the PDZ domain folds faster and independently from the SH3-GK tandem. However, concurrent folding of the PDZ domain slows down folding of SH3-GK, resulting in an off-pathway folding intermediate. This contributes to the understanding of multidomain protein folding where individual domains cannot be viewed as separate folding units.
JOURNAL OF MOLECULAR BIOLOGY
(2021)
Article
Microbiology
Kun Jiang, Weixun Li, Ming Tong, Jinghua Xu, Zhe Chen, Yan Yang, Yuanrong Zang, Xuyao Jiao, Chang Liu, Bentley Lim, Xianzhi Jiang, Jiawei Wang, Dalei Wu, Mingyu Wang, Shuang-Jiang Liu, Feng Shao, Xiang Gao
Summary: In this study, it was discovered that the gut symbiont Bacteroides fragilis secretes a toxic substance called BfUbb that lyses specific B. fragilis strains by binding and inactivating an essential peptidyl-prolyl isomerase (PPIase). The sensitivity of B. fragilis strains to BfUbb was found to be influenced by a specific tyrosine residue in the PPIase. The findings also suggest that BfUbb confers a competitive advantage for encoding strains.
NATURE MICROBIOLOGY
(2023)
Article
Multidisciplinary Sciences
Michael J. Roy, Minglyanna G. Surudoi, Ashleigh Kropp, Jianmei Hou, Weiwen Dai, Joshua M. Hardy, Lung-Yu Liang, Thomas R. Cotton, Bernhard C. Lechtenberg, Toby A. Dite, Xiuquan Ma, Roger J. Daly, Onisha Patel, Isabelle S. Lucet
Summary: PEAK pseudokinases regulate cell migration, invasion and proliferation by recruiting key signaling proteins to the cytoskeleton. The researchers elucidate the molecular details of key PEAK signaling interactions with the adapter proteins CrkII and Grb2 and the scaffold protein 14-3-3. They identify a conserved high affinity 14-3-3 motif on PEAK3 and demonstrate its role as a molecular switch to regulate CrkII binding and signaling via Grb2.
NATURE COMMUNICATIONS
(2023)
Article
Biochemistry & Molecular Biology
Fenggui Fan, Hao Zhang, Qian Wei, Yahui Wei
Summary: This study reveals the evolutionary conservation of PDI-S between land plants and algal organisms, and elucidates the induction mechanism of AtPDI11 under ER stress and the crucial importance of the D domain for its activity.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Paola Turina, Piero Fariselli, Emidio Capriotti
Summary: The study of protein folding is crucial for understanding protein function and the relationship between genetics and phenotypes. K-Pro is a new database that collects experimental kinetic data on monomeric proteins with a two-state folding mechanism. It provides a user-friendly interface for browsing and downloading relevant data.
JOURNAL OF MOLECULAR BIOLOGY
(2023)
Article
Chemistry, Physical
Furyal Ahmed, Xin-Qiu Yao, Donald Hamelberg
Summary: This study compares the conformational dynamics of cyclophilin isoforms and identifies key dynamic residues in the gatekeeper 2 region that are essential for their catalytic activity. The highly conserved glycine residue (Gly80) is predicted to contribute to the local flexibility, which is further confirmed by molecular dynamics simulations on mutants (G80A) of CypE and CypA. The mutations lead to changes in flexibility and catalytic behavior of CypE and CypA, suggesting a loss of function.
JOURNAL OF PHYSICAL CHEMISTRY B
(2023)
Article
Cell Biology
Stefan Preisendoerfer, Yoshihiro Ishikawa, Elisabeth Hennen, Stephan Winklmeier, Jonas C. Schupp, Larissa Knueppel, Isis E. Fernandez, Leonhard Binzenhofer, Andrew Flatley, Brenda M. Juan-Guardela, Clemens Ruppert, Andreas Guenther, Marion Frankenberger, Rudolf A. Hatz, Nikolaus Kneidinger, Jurgen Behr, Regina Feederle, Aloys Schepers, Anne Hilgendorff, Naftali Kaminski, Edgar Meinl, Hans Peter Baechinger, Oliver Eickelberg, Claudia A. Staab-Weijnitz
Summary: The study reveals that FKBP11 plays an important role in plasma cells, is regulated by XBP1, and sheds light on the important mechanisms involved in antibody production and folding.
Article
Multidisciplinary Sciences
Markus Blatter, Charlotte Meylan, Antoine Clery, Roberto Giambruno, Yaroslav Nikolaev, Michel Heidecker, Jessica Arvindbhai Solanki, Manuel O. Diaz, Davide Gabellini, Frederic H. -T. Allain
Summary: The study found that Mixed-lineage leukemia 1 (MLL1) is a transcription activator of the HOX family and its activity is repressed by cyclophilin 33 (Cyp33), which binds to MLL1 PHD3. The researchers determined the solution structures of Cyp33 in different binding states and identified that conformational changes triggered by Cyp33 binding to RNA facilitate the release of MLL1 from the histone mark. These findings provide a mechanistic understanding of how Cyp33 binding to MLL1 switches chromatin to a transcriptional repressive state through a negative feedback loop triggered by RNA binding.
Article
Biochemistry & Molecular Biology
Leonore Novak, Maria Petrosino, Daniele Santorelli, Roberta Chiaraluce, Valerio Consalvi, Alessandra Pasquo, Carlo Travaglini-Allocatelli
Summary: A Phi value analysis was conducted on BRD2(2) to investigate its folding pathway, revealing that the C-terminal region serves as the initial folding nucleus, with the N-terminal region consolidating its structure later in the process. This indicates a hierarchical mechanism of protein folding with non-native interactions playing a significant role.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Multidisciplinary Sciences
Anna K. Orta, Nadia Riera, Yancheng E. Li, Shiho Tanaka, Hyun Gi Yun, Lada Klaic, William M. Clemons
Summary: In this study, the researchers used single-particle electron cryo-microscopy to uncover the mechanism by which bacteriophage can kill bacteria by encoding a protein antibiotic. The results were validated experimentally and provide a model for bacterial lysis and potential design of phage therapeutics.
Article
Immunology
Nikhil Ponnoor Anto, Amitha Muraleedharan, Pulak Ranjan Nath, Zuoming Sun, Chen Keasar, Etta Livneh, Alex Braiman, Amnon Altman, Kok-Fai Kong, Noah Isakov
Summary: Protein kinase C-α (PKC-α) is selectively expressed in T lymphocytes and plays a crucial role in T cell activation and proliferation. The phosphorylation of Thr(335)-Pro residue in the regulatory domain of PKC-α is important for its activation and localization at the immunological synapse. The peptidyl-prolyl cis-trans isomerase Pin1 interacts with PKC-α through the phosphorylated Thr(335)-Pro motif, and this interaction is involved in early activation events in TCR-triggered T cells.
FRONTIERS IN IMMUNOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Koji Ooka, Runjing Liu, Munehito Arai
Summary: The WSME model is a promising statistical mechanical model that can calculate the free-energy landscapes of proteins, providing a comprehensive understanding of protein folding mechanisms and structure stability. By predicting protein folding mechanisms and associated conformational changes, this model is expected to be useful in both basic research and applications.
Article
Multidisciplinary Sciences
Lulu Jiang, Pijush Chakraborty, Lushuang Zhang, Melissa Wong, Shannon E. Hill, Chelsea Joy Webber, Jenna Libera, Laura J. Blair, Benjamin Wolozin, Markus Zweckstetter
Summary: Alzheimer's disease and related tauopathies are characterized by misfolding and aggregation of the protein tau. This study demonstrates that the immunophilin FKBP12 regulates neuronal resilience by acting as a chaperone for monomeric tau. The study identifies the molecular factors involved in FKBP12's binding to tau and its influence on tau-induced neurotoxicity.
Article
Chemistry, Physical
Abhigyan Sengupta, Lorenz E. Rognoni, Ulrich Merkel, Gabriel Zoldak, Matthias Rief
Summary: Prolyl isomerization catalyzed by the PPIase enzyme plays a crucial role in cellular signaling and molecular timing. This study demonstrates a 25-fold acceleration of trans-cis isomerization rate and a stabilization effect on the cis-isomer by SlyD in a single-molecule experiment with FlnA20 protein.
JOURNAL OF PHYSICAL CHEMISTRY B
(2021)
Article
Biochemistry & Molecular Biology
Katherine A. Alexander, Allison Cote, Son C. Nguyen, Liguo Zhang, Omid Gholamalamdari, Paula Agudelo-Garcia, Enrique Lin-Shiao, K. M. A. Tanim, Joan Lim, Nicolas Biddle, Margaret C. Dunagin, Charly R. Good, Mariel R. Mendoza, Shawn C. Little, Andrew Belmont, Eric F. Joyce, Arjun Raj, Shelley L. Berger
Summary: Nuclear speckles, containing proteins and RNA involved in gene expression, play a role in regulating gene activation. The association of p53 target genes with speckles is shown to be driven by the p53 transcription factor. This regulated speckle association mechanism boosts gene expression through elevating nascent RNA amounts, involving specific domains and DNA binding of p53. The association of p53 targets with speckles results in more robust activation and occupies a distinct niche in p53 biology.
Article
Cell Biology
Roland C. Preston, Roman P. Jakob, Florian P. C. Binder, Christoph P. Sager, Beat Ernst, Timm Maier
JOURNAL OF MOLECULAR CELL BIOLOGY
(2016)
Article
Multidisciplinary Sciences
Dominik A. Herbst, Roman P. Jakob, Franziska Zaehringer, Timm Maier
Article
Multidisciplinary Sciences
Maximilian M. Sauer, Roman P. Jakob, Jonathan Eras, Sefer Baday, Deniz Eris, Giulio Navarra, Simon Berneche, Beat Ernst, Timm Maier, Rudi Glockshuber
NATURE COMMUNICATIONS
(2016)
Article
Biochemistry & Molecular Biology
Dominik A. Herbst, Callie R. Huitt-Roehl, Roman P. Jakob, Jacob M. Kravetz, Philip A. Storm, Jamie R. Alley, Craig A. Townsend, Timm Maier
NATURE CHEMICAL BIOLOGY
(2018)
Article
Chemistry, Multidisciplinary
Christoph P. Sager, Brigitte Fiege, Pascal Zihlmann, Raghu Vannam, Said Rabbani, Roman P. Jakob, Roland C. Preston, Adam Zalewski, Timm Maier, Mark W. Peczuh, Beat Ernst
Article
Multidisciplinary Sciences
Roman P. Jakob, Philipp A. M. Schmidpeter, Johanna R. Koch, Franz X. Schmid, Timm Maier
Article
Biology
M. Alessandra Vigano, Dimitri Bieli, Jonas Schaefer, Roman P. Jakob, Shinya Matsuda, Timm Maier, Andreas Pluckthun, Markus Affolter
Article
Immunology
Marco Kuenzli, David Schreiner, Tamara C. Pereboom, Nivedya Swarnalekha, Ludivine C. Litzler, Jonas Loetscher, Yusuf I. Ertuna, Julien Roux, Florian Geier, Roman P. Jakob, Timm Maier, Christoph Hess, Justin J. Taylor, Carolyn G. King
SCIENCE IMMUNOLOGY
(2020)
Article
Multidisciplinary Sciences
Ricardo D. Righetto, Leonie Anton, Ricardo Adaixo, Roman P. Jakob, Jasenko Zivanov, Mohamed-Ali Mahi, Philippe Ringler, Torsten Schwede, Timm Maier, Henning Stahlberg
NATURE COMMUNICATIONS
(2020)
Article
Multidisciplinary Sciences
Hundeep Kaur, Roman P. Jakob, Jan K. Marzinek, Robert Green, Yu Imai, Jani Reddy Bolla, Elia Agustoni, Carol Robinson, Peter J. Bond, Kim Lewis, Timm Maier, Sebastian Hiller
Summary: Developing new antibiotics that target Gram-negative bacteria is crucial for addressing the antimicrobial resistance crisis. Through studying the mode of action of darobactin at the atomic level, it was revealed that darobactin can bind to the lateral gate of BamA with superior ability, highlighting the lateral gate as a functional hotspot in BamA.
Article
Multidisciplinary Sciences
Yves U. Tittes, Dominik A. Herbst, Solene F. X. Martin, Hugo Munoz-Hernandez, Roman P. Jakob, Timm Maier
Summary: Polyketide synthases (PKSs) are microbial biosynthetic enzymes that can assemble potent bioactive natural products. The modular architecture of PKS assembly lines plays a crucial role in substrate transfer and enzyme sequestration.
Article
Biochemistry & Molecular Biology
Lei Zhang, Marina Toplak, Raspudin Saleem-Batcha, Lars Hoeing, Roman Jakob, Nico Jehmlich, Martin von Bergen, Timm Maier, Robin Teufel
Summary: Antimicrobial resistance is a serious threat to human health, and understanding the underlying mechanisms is crucial. This study discovered and characterized oxidoreductases that inactivate the broad-spectrum antibiotic chloramphenicol through dual oxidation of the C3-hydroxyl group. These enzymes also enable the inactivation of related compounds but not the fluorinated derivative. Phylogenetic analyses suggest that distinct isofunctional enzymes evolved independently in Gram-positive and Gram-negative bacteria. Mechanistic and structural studies provide insights into the catalytic mechanisms of these enzymes, which have both negative and positive impacts on antibiotic resistance and chloramphenicol bioremediation.
Article
Biochemistry & Molecular Biology
Jonathan Cramer, Xiaohua Jiang, Wojciech Schoenemann, Marleen Silbermann, Pascal Zihlmann, Stefan Siegrist, Brigitte Fiege, Roman Peter Jakob, Said Rabbani, Timm Maier, Beat Ernst
RSC CHEMICAL BIOLOGY
(2020)
Correction
Multidisciplinary Sciences
Ricardo D. Righetto, Leonie Anton, Ricardo Adaixo, Roman P. Jakob, Jasenko Zivanov, Mohamed-Ali Mahi, Philippe Ringler, Torsten Schwede, Timm Maier, Henning Stahlberg
NATURE COMMUNICATIONS
(2020)
Article
Biochemistry & Molecular Biology
Giulio Navarra, Pascal Zihlmann, Roman P. Jakob, Katja Stangier, Roland C. Preston, Said Rabbani, Martin Smiesko, Bea Wagner, Timm Maier, Beat Ernst
Article
Biochemistry & Molecular Biology
Ankita Chadda, Alexander G. Kozlov, Binh Nguyen, Timothy M. Lohman, Eric A. Galburt
Summary: In this study, it was found that the DNA damage response in Mycobacterium tuberculosis differs from well-studied model bacteria. The DNA repair helicase UvrD1 in Mtb is activated through a redox-dependent process and is closely associated with the homo-dimeric Ku protein. Additionally, Ku protein is shown to stimulate the helicase activity of UvrD1.
JOURNAL OF MOLECULAR BIOLOGY
(2024)