Article
Cell Biology
Josephine Alba, Marco D'Abramo
Summary: Studies have shown that a conformational change occurs in the TCR after binding to pMHC, with the TCR Constant beta (C beta) region playing a key role in signal propagation. Additionally, it was found that TCR reduces the flexibility of the MHC I binding groove.
Article
Biochemistry & Molecular Biology
Shoutang Wang, Raki Sudan, Vincent Peng, Yingyue Zhou, Siling Du, Carla M. Yuede, Tingting Lei, Jinchao Hou, Zhangying Cai, Marina Cella, Khai Nguyen, Pietro L. Poliani, Wandy L. Beatty, Yun Chen, Siyan Cao, Kent Lin, Cecilia Rodrigues, Ali H. Ellebedy, Susan Gilfillan, Gordon D. Brown, David M. Holtzman, Simone Brioschi, Marco Colonna
Summary: Genetic studies have shown that microglia play a crucial role in Alzheimer's disease (AD). Microglia that attach to Ab plaques have a transcriptional signature called disease-associated microglia (DAM), which mainly comes from the TREM2-DAP12 receptor complex that signals through the protein tyrosine kinase SYK. The human TREM2R47H variant, associated with a high risk of AD, fails to activate microglia via SYK.
Article
Multidisciplinary Sciences
Gaurav Kumar, Prateek Chawla, Neha Dhiman, Sanya Chadha, Sheetal Sharma, Kanupriya Sethi, Mahak Sharma, Amit Tuli
Summary: The bidirectional movement of lysosomes is regulated by Arl8b and its effector RUFY3, which control the anterograde and retrograde transport of lysosomes, as well as their positioning and size in cells.
NATURE COMMUNICATIONS
(2022)
Article
Multidisciplinary Sciences
Martina Barends, Nicole Koller, Christian Schoelz, Veronica Duran, Berislav Bosnjak, Jennifer Becker, Marius Doering, Hanna Blees, Reinhold Foerster, Ulrich Kalinke, Robert Tampe
Summary: By studying human dendritic cells, we discovered that additional proteins are recruited to the peptide-loading complex (PLC) during dendritic cell differentiation and maturation, including BAP31, VAPA, and ESYT1. These proteins colocalize with TAP and are in close proximity to the PLC, indicating that the antigen processing machinery is located near ER exit- and membrane contact sites.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Cell Biology
Etienne Leveille, Lai N. Chan, Abu-Sayeef Mirza, Kohei Kume, Markus Muschen
Summary: SYK and ZAP70 nonreceptor tyrosine kinases play essential roles in B-cell and T-cell signaling. Aberrant co-expression of ZAP70 with SYK is found in B-cell malignancies and has oncogenic effects by redirecting downstream signaling. Developmental separation of these kinases is crucial for preventing pathological cell survival.
CELLULAR SIGNALLING
(2022)
Article
Chemistry, Physical
Mingzhen Zhang, Yonglan Liu, Hyunbum Jang, Ruth Nussinov
Summary: Kinase drug selectivity is a challenge in cancer research. Researchers propose a protocol to identify unique geometric features in the drug pocket that can distinguish one kinase from others. They analyze the structural principles of kinase drug selectivity using experimental structures and artificial intelligence. The results show that there are binary units in the kinome that can distinguish kinases from each other.
JOURNAL OF CHEMICAL THEORY AND COMPUTATION
(2023)
Article
Chemistry, Medicinal
Brian T. Hopkins, Eris Bame, Bekim Bajrami, Cheryl Black, Tonika Bohnert, Carrie Boiselle, Doug Burdette, Jeremy C. Burns, Luisette Delva, Douglas Donaldson, Richard Grater, Chungang Gu, Marc Hoemberger, Josh Johnson, Sudarshan Kapadnis, Kris King, Mukesh Lulla, Bin Ma, Isaac Marx, Tom Magee, Robert Meissner, Claire M. Metrick, Michael Mingueneau, Paramasivam Murugan, Kevin L. Otipoby, Evelyne Polack, Urjana Poreci, Robin Prince, Allie M. Roach, Chris Rowbottom, Joseph C. Santoro, Patricia Schroeder, Hao Tang, Eric Tien, Fengmei Zhang, Joseph Lyssikatos
Summary: Multiple Sclerosis is a chronic autoimmune neurodegenerative disorder that leads to permanent disability. The discovery of BIIB091 as a selective, reversible drug provides a potential treatment option for MS.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Cell Biology
Wei-Qing Shao, Wen-Wei Zhu, Meng-Jun Luo, Ming-Hao Fan, Qin Li, Sheng-Hao Wang, Zhi-Fei Lin, Jing Zhao, Yan Zheng, Qiong-Zhu Dong, Lu Lu, Hu-Liang Jia, Ju-Bo Zhang, Ming Lu, Jin-Hong Chen, Lun-Xiu Qin
Summary: This study reveals that cholesterol suppresses the autophagic degradation of RTKs in a GOLM1-dependent manner, and lowering cholesterol by statins can enhance the efficacy of multiple tyrosine kinase inhibitors in HCC.
Article
Multidisciplinary Sciences
Ming-Yuan Su, Simon A. Fromm, Jonathan Remis, Daniel B. Toso, James H. Hurley
Summary: Mutation of C9ORF72 is a common genetic cause of ALS and FTD, leading to both gain and loss of function. The C9orf72 complex with SMCR8 and WDR41 has GAP activity for ARF family proteins and RAB proteins. The study provides evidence for the specific function of the C9orf72 complex as an ARF GAP and a structural framework for the longin-containing GAP family.
NATURE COMMUNICATIONS
(2021)
Article
Biochemistry & Molecular Biology
Dabbugoddu Brahmaiah, Anagani Kanaka Durga Bhavani, Pasula Aparna, Nangunoori Sampath Kumar, Helene Solhi, Remy Le Guevel, Blandine Baratte, Thomas Robert, Sandrine Ruchaud, Stephane Bach, Surender Singh Jadav, Chada Raji Reddy, Paul Mosset, Nicolas Gouault, Nicolas Levoin, Rene Gree
Summary: Three series of CLK1 inhibitors were designed, synthesized, and tested against CLKs and DYRK1A kinases. A promising derivative 12g was discovered, showing significant inhibition activity against HsCLK1 and HsDYRK1A. Molecular modeling and kinome scan analysis further supported these results, suggesting the potential for developing selective inhibitors in this kinase family.
Article
Chemistry, Medicinal
Christian G. Kurz, Franziska Preuss, Amelie Tjaden, Martin Cusack, Jennifer Alisa Amrhein, Deep Chatterjee, Sebastian Mathea, Lena Marie Berger, Benedict-Tilman Berger, Andreas Kramer, Michael Weller, Tobias Weiss, Susanne Mueller, Stefan Knapp, Thomas Hanke
Summary: Serine/threonine kinase 17A (DRAK1) belongs to the dark kinome family and its cellular function and involvement in pathophysiological processes are not well understood. This study optimized a potential DRAK1 inhibitor CK156, which showed high potency and selectivity in vitro. However, the inhibition of cell growth in glioma cells was observed only at low micromolar concentrations.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Liping Liu, Richard M. Lucas, Jeffrey D. Nanson, Yan Li, Jason Whitfield, James E. B. Curson, Neeraj Tuladhar, Kirill Alexandrov, Mehdi Mobli, Matthew J. Sweet, Bostjan Kobe, Jennifer L. Stow, Lin Luo
Summary: In this study, we identify a novel immune-specific Syk scaffold protein SCIMP, which can contribute to inflammation through selective TLR-driven inflammatory responses.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Multidisciplinary Sciences
Alida Besch, William M. Marsiglia, Moosa Mohammadi, Yingkai Zhang, Nathaniel J. Traaseth
Summary: Many human cancers are treated with small molecule inhibitors that target the kinase domain of receptor tyrosine kinases. Long-term treatment often leads to drug resistance mutations at the gatekeeper residue, increasing the aggressiveness of the cancer. However, the mechanism of gain-of-function by gatekeeper mutations is poorly understood.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Oncology
Tamas Kovacs, Florina Zakany, Peter Nagy
Summary: This paper provides a concise overview of how receptor tyrosine kinases are activated and their association with cancer. Understanding the regulation of cell fate and motility can potentially lead to advancements in cancer treatment. The role of lipid-protein interactions in receptor activation is also discussed.
Article
Biochemistry & Molecular Biology
Tufail Ali, Farah Anjum, Arunabh Choudhury, Alaa Shafie, Amal Adnan Ashour, Abdulraheem Almalki, Taj Mohammad, Md. Imtaiyaz Hassan
Summary: Spleen tyrosine kinase (SYK) is a non-receptor tyrosine kinase that plays a crucial role in signal transduction in different cell types. In this study, two natural compounds, Isolysergic acid and Michelanugine, were identified as potential SYK inhibitors with strong affinity and specificity for the SYK binding pocket. These compounds have the potential to be developed into promising SYK inhibitors for the treatment of autoimmune disorders, cancer, and inflammatory diseases.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Article
Chemistry, Medicinal
Stefan M. Ivanov, Roland G. Huber, Irfan Alibay, Jim Warwicker, Peter J. Bond
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2019)
Article
Biochemistry & Molecular Biology
Kamal Kant Sharma, Xin-Xiang Lim, Sarala Neomi Tantirimudalige, Anjali Gupta, Jan K. Marzinek, Daniel Holdbrook, Xin Ying Elisa Lim, Peter J. Bond, Ganesh S. Anand, Thorsten Wohland
Article
Multidisciplinary Sciences
Roland G. Huber, Xin Ni Lim, Wy Ching Ng, Adelene Y. L. Sim, Hui Xian Poh, Yang Shen, Su Ying Lim, Karin B. Sundstrom, Xuyang Sun, Jong Ghut Aw, Horng Khit Too, Peng Hee Boey, Andreas Wilm, Tanu Chawla, Milly M. Choy, Lu Jiang, Paola Florez de Sessions, Xian Jun Loh, Sylvie Alonso, Martin Hibberd, Niranjan Nagarajan, Eng Eong Ooi, Peter J. Bond, October M. Sessions, Yue Wan
NATURE COMMUNICATIONS
(2019)
Article
Biochemistry & Molecular Biology
Alexander Krah, Jan K. Marzinek, Peter J. Bond
BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES
(2019)
Article
Microbiology
Xin-Ni Lim, Chao Shan, Jan K. Marzinek, Hongping Dong, Thiam Seng Ng, Justin S. G. Ooi, Guntur Fibriansah, Jiaqi Wang, Chandra S. Verma, Peter J. Bond, Pei-Yong Shi, Shee-mei Lok
Article
Biochemistry & Molecular Biology
Alexander Krah, Roland G. Huber, Ulrich Zachariae, Peter J. Bond
BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES
(2020)
Article
Chemistry, Physical
Alexander Krah, Roland G. Huber, Peter J. Bond
Article
Biochemistry & Molecular Biology
Jitka Petrlova, Ganna Petruk, Roland G. Huber, Eilish W. McBurnie, Mariena J. A. van der Plas, Peter J. Bond, Manoj Puthia, Artur Schmidtchen
JOURNAL OF BIOLOGICAL CHEMISTRY
(2020)
Article
Medicine, General & Internal
Li Kiang Tan, Wing Yan Wong, Hui Ting Yang, Roland G. Huber, Peter J. Bond, Lee Ching Ng, Sebastian Maurer-Stroh, Hapuarachchige Chanditha Hapuarachchi
Review
Biochemistry & Molecular Biology
Jan K. Marzinek, Roland G. Huber, Peter J. Bond
CURRENT OPINION IN STRUCTURAL BIOLOGY
(2020)
Article
Biochemistry & Molecular Biology
Kwok-Fong Chan, Chinh Tran-To Su, Alexander Krah, Ser-Xian Phua, Joshua Yi Yeo, Wei-Li Ling, Peter J. Bond, Samuel Ken-En Gan
Article
Biochemistry & Molecular Biology
Ganna Petruk, Jitka Petrlova, Firdaus Samsudin, Rita Del Giudice, Peter J. Bond, Artur Schmidtchen
Article
Biochemistry & Molecular Biology
Manoj Puthia, Jan K. Marzinek, Ganna Petruk, Gizem Erturk Bergdahl, Peter J. Bond, Jitka Petrlova
Summary: This study demonstrates that APOE has anti-bacterial activity against several Gram-negative bacterial strains and exhibits significant binding affinity for lipopolysaccharide and heparin. Molecular dynamics simulations reveal the binding region in helix 4 of APOE as a primary site for interaction with these molecules through electrostatic interactions.
Article
Biochemistry & Molecular Biology
Priscilla L. S. Boon, Ana S. Martins, Xin Ni Lim, Francisco J. Enguita, Nuno C. Santos, Peter J. Bond, Yue Wan, Ivo C. Martins, Roland G. Huber
Summary: Dengue virus is a significant health risk in tropical and subtropical regions. The structure of the packaged genome in complex with C proteins remains elusive. This study investigates the interactions of C proteins with viral RNA and shows their role in coordinating key interactions for proper packaging of viral RNA.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Chemistry, Multidisciplinary
Firdaus Samsudin, Joshua Yi Yeo, Samuel Ken-En Gan, Peter J. Bond