Article
Multidisciplinary Sciences
Karin Legerstee, Tsion E. Abraham, Wiggert A. van Cappellen, Alex L. Nigg, Johan A. Slotman, Adriaan B. Houtsmuller
Summary: Focal adhesions (FAs) are flat elongated structures consisting of three layers along the vertical axis. Different proteins extend at different parts of the FAs, and their redistribution may be involved in cell movement during migration processes.
SCIENTIFIC REPORTS
(2021)
Article
Biochemistry & Molecular Biology
Ingo Thievessen, Frank Suhr, Silvia Vergarajauregui, Ralph T. Bottcher, Klara Brixius, Georg Rosenberger, Oliver Dewald, Bernd K. Fleischmann, Alexander Ghanem, Marcus Kruger, Felix B. Engel, Ben Fabry, Wilhelm Bloch, Reinhard Fassler
Summary: This study identifies beta-parvin as a novel mechano-responsive signaling hub in hypertrophic cardiomyocytes that drives cell elongation in response to physiological mechanical loads.
Article
Biochemistry & Molecular Biology
Eleni Michael, Savvas Polydorides, Vasilis J. Promponas, Paris Skourides, Georgios Archontis
Summary: Novel approaches for inhibiting FAK and PYK2 involve interfering with protein interactions promoting localization at FAs, validated by techniques such as surface plasmon resonance and fluorescence polarization assays. Molecular dynamics simulations provide insights into the recognition of peptides with LD motifs by FAK-FAT and PYK2-FAT domains, aiding in the design of inhibitory peptides and pharmacophore models for potential small-molecule inhibitors.
PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS
(2021)
Article
Multidisciplinary Sciences
Michael S. Hwang, Michelle S. Miller, Puchong Thirawatananond, Jacqueline Douglass, Katharine M. Wright, Emily Han-Chung Hsiue, Brian J. Mog, Tihitina Y. Aytenfisu, Michael B. Murphy, P. Aitana Azurmendi, Andrew D. Skora, Alexander H. Pearlman, Suman Paul, Sarah R. DiNapoli, Maximilian F. Konig, Chetan Bettegowda, Drew M. Pardoll, Nickolas Papadopoulos, Kenneth W. Kinzler, Bert Vogelstein, Shibin Zhou, Sandra B. Gabelli
Summary: The study describes the development of CAR T cells targeting a tumor-specific neoantigen presented on the cell surface, improving sensitivity and specificity through engineering and optimization of the targeting moiety. This approach shows promise for immunotherapies targeting difficult-to-reach cancer driver mutations.
NATURE COMMUNICATIONS
(2021)
Article
Cell Biology
Ioanna Antoniades, Maria Kyriakou, Anna Charalambous, Katerina Kalalidou, Andri Christodoulou, Maria Christoforou, Paris A. Skourides
Summary: The study successfully prevented the action of FAK at focal adhesions by generating a specific peptide structure, thereby effectively inhibiting the migration and invasion of tumor cells and providing a new direction for the development of anti-metastatic agents.
CELL COMMUNICATION AND SIGNALING
(2021)
Article
Biology
Haibin Yang, Leishu Lin, Kang Sun, Ting Zhang, Wan Chen, Lianghui Li, Yuchen Xie, Chuanyue Wu, Zhiyi Wei, Cong Yu
Summary: The study demonstrates that Rsu1 negatively modulates F-actin bundling by interacting with the IPP complex, disrupting the binding of PINCH1 to actin.
Article
Multidisciplinary Sciences
Sarah A. Mosure, Timothy S. Strutzenberg, Jinsai Shang, Paola Munoz-Tello, Laura A. Solt, Patrick R. Griffin, Douglas J. Kojetin
Summary: Heme is an endogenous ligand for REV-ERB nuclear receptors, regulating their activity by binding with corepressor NCoR and influencing the thermodynamic interaction profile between NCoR and REV-ERBβ. This finding sheds light on the mechanism of heme-dependent REV-ERB activity.
Article
Multidisciplinary Sciences
Fan Lu, Liang Zhu, Thomas Bromberger, Jun Yang, Qiannan Yang, Jianmin Liu, Edward F. Plow, Markus Moser, Jun Qin
Summary: The authors report a mechanism in which talin and kindlin are bridged by paxillin to induce microclustering of integrins, leading to potent binding between integrins and extracellular ligands. The study also reveals that the C-terminal rod domain of talin enhances its potency in activating integrins by dimerizing activated talin and bridging it to the integrin co-activator kindlin-2 via paxillin. This study provides crucial insights into the mechanism of talin and its cooperation with kindlin in promoting integrin activation and cell adhesion.
NATURE COMMUNICATIONS
(2022)
Article
Immunology
Jing Yang, Sheng Lin, Honglu Sun, Zimin Chen, Fanli Yang, Xi Lin, Liyan Guo, Lingling Wang, Ao Wen, Xindan Zhang, Yushan Dai, Bin He, Yu Cao, Haohao Dong, Xianbo Liu, Bo Chen, Jian Li, Qi Zhao, Guangwen Lu
Summary: This study identifies a potent neutralizing nanobody, Nb-007, against SARS-CoV-2. Nb-007 exhibits excellent virus entry-inhibition activity by competing with ACE2 for viral binding. Furthermore, fusion with Fc significantly enhances its entry-inhibition capacity.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Chuan Guo, Qinxuan Li, Jiujia Xiao, Feng Ma, Xun Xia, Mingsong Shi
Summary: This study improves our understanding of the binding mechanism between human FAK and VS-6063 by constructing a binding model and analyzing key residues. Furthermore, novel compounds have been designed for future drug development targeting FAK.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Article
Biochemistry & Molecular Biology
Qianqian He, Siu Kwan Sze, Kai Soon Ng, Cheng-Gee Koh
Summary: The composition of focal adhesions (FAs) in mouse embryonic stem cells (mESCs) is similar to that of differentiated cells, but the maturation of FAs is less in mESCs. The combination of different quantitative proteomics methods allows for a comprehensive and targeted analysis of the molecular composition of FAs in mESCs.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2023)
Review
Biochemistry & Molecular Biology
Xiao-Jing Pang, Xiu-Juan Liu, Yuan Liu, Wen-Bo Liu, Yin-Ru Li, Guang-Xi Yu, Xin-Yi Tian, Yan-Bing Zhang, Jian Song, Cheng-Yun Jin, Sai-Yang Zhang
Summary: FAK, a nonreceptor intracellular tyrosine kinase, is overexpressed in many human cancer cell lines, promoting tumor growth by controlling various cellular functions. Targeting FAK with small molecule inhibitors is considered a promising cancer therapy, with several FAK inhibitors undergoing clinical trials in different phases. Additionally, the development of novel FAK inhibitors, including FAK degraders through PROTAC technology, provides potential for new anticancer agents.
Article
Chemistry, Multidisciplinary
Katherine A. Morgan, Michael de Veer, Luke A. Miles, Cormac A. A. Kelderman, Catriona A. McLean, Colin L. Masters, Kevin J. Barnham, Jonathan M. White, Brett M. Paterson, Paul S. Donnelly
Summary: To develop a diagnostic method for Alzheimer's disease, two antibodies specific for amyloid-beta were modified and two compounds with pendant 1,2,4,5-tetrazine groups were labelled with copper-64. The copper-64 complexes reacted with the modified antibodies in a click reaction and crossed the blood-brain barrier in mice.
CHEMICAL COMMUNICATIONS
(2023)
Article
Multidisciplinary Sciences
Yiwei Chen, Kai Xu, Luca Piccoli, Mathilde Foglierini, Joshua Tan, Wenjie Jin, Jason Gorman, Yaroslav Tsybovsky, Baoshan Zhang, Boubacar Traore, Chiara Silacci-Fregni, Claudia Daubenberger, Peter D. Crompton, Roger Geiger, Federica Sallusto, Peter D. Kwong, Antonio Lanzavecchia
Summary: This study demonstrates that Plasmodium falciparum RIFINs can bind to LILRB1 through D3, and inserting receptor domains into the VH-CH1 elbow can generate novel antibodies, as shown by a naturally selected example.
Article
Biochemistry & Molecular Biology
Peng Wang, Jing Zhao, Seyedmehdi Hossaini Nasr, Sarah A. Otieno, Fuming Zhang, Wei Qiang, Robert J. Linhardt, Xuefei Huang
Summary: The highly sulfated HS oligosaccharides show the strongest binding affinity with A beta and can reduce cellular toxicities induced by A beta. Elongating the glycan length significantly enhances A beta affinity. This study provides new insights into HS/A beta interactions.
ACS CHEMICAL BIOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Yasmin A. Kadry, David A. Calderwood
BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES
(2020)
Article
Biochemistry & Molecular Biology
Yasmin A. Kadry, Eesha M. Maisuria, Clotilde Huet-Calderwood, David A. Calderwood
JOURNAL OF BIOLOGICAL CHEMISTRY
(2020)
Article
Multidisciplinary Sciences
Mo Zhou, Leena Kuruvilla, Xiarong Shi, Stephen Viviano, Ian M. Ahearn, Caroline R. Amendola, Wenjuan Su, Sana Badri, James Mahaffey, Nicole Fehrenbacher, Jane Skok, Joseph Schlessinger, Benjamin E. Turk, David A. Calderwood, Mark R. Philips
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2020)
Article
Multidisciplinary Sciences
Richard B. Gillis, Hodaya Solomon, Lata Govada, Neil J. Oldham, Vlad Dinu, Shahwar Imran Jiwani, Philemon Gyasi-Antwi, Frank Coffey, Andy Meal, Paul S. Morgan, Stephen E. Harding, John R. Helliwell, Naomi E. Chayen, Gary G. Adams
Summary: The study into the rapid-acting insulin analogue glulisine using a combination of X-ray crystallography and biophysical characterisation provided insights into its structure and function, potentially leading to a better understanding of its pharmacokinetic and pharmacodynamic behavior.
SCIENTIFIC REPORTS
(2021)
Article
Chemistry, Multidisciplinary
Christo Nanev, Lata Govada, Naomi E. Chayen
Summary: This study explains the nucleation ability of pores by balancing the cohesive energy maintaining the integrity of a crystalline cluster with the destructive energy tending to tear it up. It also demonstrates the importance of having 2D crystals nucleating in the pores first in order to obtain 3D crystals. By filling the pore orifice, the stability of 2D crystal nuclei is increased, as their peripheries are protected from the destructive action of water molecules.
Article
Cell Biology
Eunice Cho, Hua Jane Lou, Leena Kuruvilla, David A. Calderwood, Benjamin E. Turk
Summary: This study identifies PPP6C as a crucial phosphatase for MEK in the ERK pathway, which is frequently mutated or downregulated in melanoma. Loss of PPP6C leads to hyperphosphorylation of MEK, enhancing signaling through the pathway and reducing sensitivity to MEK inhibitors. Its recurrent mutations in melanoma cause MEK hyperphosphorylation, suggesting their role in promoting the disease by activating the core oncogenic pathway.
Article
Immunology
Virtu Solano-Collado, Rosa Angela Colamarino, David A. Calderwood, Massimiliano Baldassarre, Stefania Spano
Summary: Salmonella Typhi is a human-restricted bacterial pathogen that can survive in human macrophages but not in macrophages from other animals. An optimized experimental method for shRNA screening has been developed to identify genes controlling the growth of S. Typhi in macrophages, providing insights into host-restriction mechanisms.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2021)
Article
Chemistry, Multidisciplinary
Lata Govada, Emmanuel Saridakis, Sean C. Kassen, Ahmad Bin-Ramzi, Rhodri Marc Morgan, Benjamin Chain, John R. Helliwell, Naomi E. Chayen
Summary: CCR5 is a major co-receptor molecule used by HIV-1 to enter cells. X-ray crystallographic studies of the anti-CCR5 antibody RoAb13 together with two peptides suggested a potential blocking effect on HIV entry. This may be useful in the design of a new biomimetic to stimulate an antibody response to CCR5 and block HIV infection.
Article
Biochemical Research Methods
Kezzia S. Jones, Amanda E. Chapman, Holland A. Driscoll, Emily P. Fuller, Meghan Kelly, Xiaofeng Li, Sourour Mansour, Shannon L. McBride, Qi Zhao, Michael Weiner, Mary R. Ferguson
Summary: Antibody validation is crucial for sensitivity and specificity in a given application, especially against post-translationally modified targets. A novel validation method using surrogate proteins called 'MILKSHAKE' has been developed for Western blot, allowing for confirmation of antibody specificity. This method can also be used for non-PTMs targets, demonstrating its versatility.
Article
Multidisciplinary Sciences
Bertrand Simon, Hua Jane Lou, Clotilde Huet-Calderwood, Guangda Shi, Titus J. Boggon, Benjamin E. Turk, David A. Calderwood
Summary: TLK2 selectively targets ASF1 by mimicking its client protein histone H3, promoting nucleosome assembly. This selectivity is achieved through recognition of phosphorylation site motifs in ASF1 by the catalytic domain of TLK2 and interaction between a short sequence at the N-terminus of TLK2 and the N-terminal domain of ASF1.
NATURE COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Christo N. Nanev, Emmanuel Saridakis, Lata Govada, Naomi E. Chayen
Summary: Growing protein crystals using porous materials can improve diffraction quality, and crystals continue to grow outside the pores after nucleation inside them.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Cell Biology
Pakorn Kanchanawong, David A. Calderwood
Summary: Cell-extracellular matrix (ECM) interactions occur at specialized, multi-protein adhesion complexes, with clustered integrins as the predominant ECM receptors. Progress in characterization of adhesion composition, organization and dynamics in response to force has improved understanding of adhesion maturation and turnover and the relationships between adhesion structures and functions.
NATURE REVIEWS MOLECULAR CELL BIOLOGY
(2023)
Article
Cell Biology
Clotilde Huet-Calderwood, Felix E. Rivera-Molina, Derek K. Toomre, David A. Calderwood
Summary: Fibronectin (FN) is an important component of the extracellular matrix (ECM) that supports cell adhesion, migration, and signaling through binding to integrin receptors. This study demonstrates that FN is secreted predominantly at the ventral surface of cells in an integrin-independent manner and its secretion is regulated by cell polarization. Additionally, the deposition of FN continues during focal adhesion disassembly.
JOURNAL OF CELL BIOLOGY
(2022)
Article
Biology
Byung Hak Ha, Sezin Yigit, Nalini Natarajan, Elizabeth M. Morse, David A. Calderwood, Titus J. Boggon
Summary: This study investigates the interaction between integrin β5 and PAK4, revealing the molecular basis of their interaction and the inhibitory effect of integrin β5 on PAK4 activity.
COMMUNICATIONS BIOLOGY
(2022)
Correction
Biology
Byung Hak Ha, Sezin Yigit, Nalini Natarajan, Elizabeth M. Morse, David A. Calderwood, Titus J. Boggon
COMMUNICATIONS BIOLOGY
(2023)