Review
Biochemistry & Molecular Biology
Amita R. Sahoo, Matthias Buck
Summary: This review focuses on the interaction between Eph receptors and ephrin ligands in regulating various processes from embryonic development to tissue homeostasis. It also highlights the importance of the transmembrane domain of Eph receptors in signal transduction and introduces techniques such as NMR and molecular modeling used to study them. Additionally, the use of transmembrane peptides to manipulate Eph receptor signaling is discussed, along with future directions for research in this field.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Biochemical Research Methods
Xia Zhang, Jiaqi Yin, Wei Pan, Yanhua Li, Na Li, Bo Tang
Summary: This review introduces the importance of receptor tyrosine kinases (RTKs) and their dimers in cell signal transduction pathways and highlights the strategies and advances in imaging RTK dimers. The visualization of RTK dimers is significant for monitoring physiological processes and expanding applications in biomedical areas.
ANALYTICAL AND BIOANALYTICAL CHEMISTRY
(2023)
Review
Cell Biology
Peiyuan Huang, Zhihao Zhao, Liting Duan
Summary: Dynamic protein-protein interactions are crucial for cell functioning, and homo-interactions are widely used to activate intracellular signaling pathways. Optogenetic tools based on light-sensitive proteins offer unprecedented specificity and spatiotemporal precision in dissecting complex signaling networks. This review focuses on recent progress in developing optogenetic tools for light-inducible protein-protein homo-interactions and their applications in optical activation of signaling pathways.
NEURAL REGENERATION RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Lisa M. Petti, Benjamin N. Koleske, Daniel DiMaio
Summary: Most eukaryotic transmembrane and secreted proteins contain N-terminal signal peptides that facilitate membrane insertion and subsequent degradation. A small hydrophobic protein can act as a signal peptide while retaining transforming activity, interacting with target protein transmembrane domains. This finding suggests that naturally occurring signal peptides may have additional biological activities.
JOURNAL OF MOLECULAR BIOLOGY
(2021)
Article
Chemistry, Multidisciplinary
Qingshan Fu, James J. Chou
Summary: The study identified the structure of the TMD of the S protein of SARS-CoV-2, revealing it as a transmembrane alpha-helix trimer that spontaneously assembles in the membrane, with a strong hydrophobic core. The research also found that, despite being highly stable, single mutations can completely dissociate this trimer.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2021)
Article
Biochemistry & Molecular Biology
Yaroslav V. V. Bershatsky, Andrey S. S. Kuznetsov, Aisha R. R. Idiatullina, Olga V. V. Bocharova, Sofya M. M. Dolotova, Alina A. A. Gavrilenkova, Oxana V. V. Serova, Igor E. E. Deyev, Tatiana V. V. Rakitina, Olga T. T. Zangieva, Konstantin V. V. Pavlov, Oleg V. V. Batishchev, Vladimir V. V. Britikov, Sergey A. A. Usanov, Alexander S. S. Arseniev, Roman G. G. Efremov, Eduard V. V. Bocharov
Summary: The InsR, IGF1R, and IRR receptor tyrosine kinases (RTK) of the insulin receptor subfamily play a crucial role in various physiological processes and are associated with several diseases, including neurodegenerative diseases. This study examines the structural and dynamic characteristics of these receptors and highlights the significant differences in their transmembrane domains and lipid interactions. The membrane-mediated control of receptor signaling offers promising opportunities for the development of targeted therapies for diseases related to insulin subfamily receptors dysfunction.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Emilie Aponte, Marie Lafitte, Audrey Sirvent, Valerie Simon, Maud Barbery, Elise Fourgous, Mariano Maffei, Florence Armand, Romain Hamelin, Julie Pannequin, Philippe Fort, Miquel Pons, Serge Roche, Yvan Boublik
Summary: This study reveals the important role of the unique domain ULBR in Src tyrosine kinase in malignant cell transformation. The ULBR is involved in membrane anchoring, MAPK signaling, and phosphorylation of specific membrane-localized tyrosine kinases needed for Src oncogenic signaling.
Review
Cell Biology
Li Chen, Xiangyi Kong, Yi Fang, Shishir Paunikar, Xiangyu Wang, James A. L. Brown, Emer Bourke, Xingrui Li, Jing Wang
Summary: Discoidin domain receptor tyrosine kinases (DDRs) are a type of receptor tyrosine kinases associated with various diseases, widely expressed in different cell types and involved in signaling pathways, closely related to the development and progression of solid tumors.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Biology
Jean-Philippe Defour, Emilie Leroy, Sharmila Dass, Thomas Balligand, Gabriel Levy, Ian C. Brett, Nicolas Papadopoulos, Celine Mouton, Lidvine Genet, Christian Pecquet, Judith Staerk, Steven O. Smith, Stefan N. Constantinescu, Lewis E. Kay
Summary: The study investigates the structural basis of activation for TpoR mutations S505N and W515K that induce myeloproliferative neoplasms. Ligand-independent activation of TpoR by TM asparagine (Asn) substitutions is shown to be proportional to the proximity of the Asn mutation to the intracellular membrane surface. The loss of helical structure in the juxtamembrane (JM) R/KWQFP motif and the effect of helical structure in the JM motif on receptor function are also investigated.
Article
Immunology
Yannick D. Muller, Duy P. Nguyen, Leonardo M. R. Ferreira, Patrick Ho, Caroline Raffin, Roxxana Valeria Beltran Valencia, Zion Congrave-Wilson, Theodore L. Roth, Justin Eyquem, Frederic Van Gool, Alexander Marson, Laurent Perez, James A. Wells, Jeffrey A. Bluestone, Qizhi Tang
Summary: This study revealed a fundamental difference between CD28-TMD and CD8-TMD, indicating that CD28-TMD can modulate CAR T-cell activities by engaging endogenous partners.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Chemistry, Physical
Ayan Majumder, John E. Straub
Summary: The widely used MARTINI model is found to over-stabilize membrane protein aggregates, leading to a reparameterization to enhance the agreement between simulation results and experimental data. The modified MARTINI model maintains a dynamic equilibrium between protein monomers and dimers.
JOURNAL OF CHEMICAL THEORY AND COMPUTATION
(2021)
Review
Chemistry, Analytical
Juan Gao, Jingyi Jian, Zhengjin Jiang, Ann Van Schepdael
Summary: Tyrosine kinases have been extensively studied as drug targets due to their regulation of cellular processes. The deregulation of tyrosine kinases plays a key role in the pathophysiology of various diseases. Several techniques, including traditional binding assays and high-throughput screening methods, have been developed to discover new tyrosine kinase inhibitors. This review provides insights into the different assay methods for the exploration of novel tyrosine kinase inhibitors.
JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
(2023)
Article
Biochemistry & Molecular Biology
Kirill E. Medvedev, R. Dustin Schaeffer, Jimin Pei, Nick V. Grishin
Summary: This study mapped pathogenic mutations in 497 human protein kinase domains to the reference structure of Aurora kinase A (AURKA) and categorized them based on disease type. The majority of cancer-related mutation hotspots were found within the catalytic and activation loops of the kinase domain, while non-cancer-related hotspots were located outside of these regions. A hotspot at residue R371 of the AURKA structure with the highest number of exclusively non-cancer-related pathogenic mutations (21) was also identified.
Article
Biochemistry & Molecular Biology
Kirill E. Medvedev, R. Dustin Schaeffer, Jimin Pei, Nick V. Grishin
Summary: The dysregulation of protein kinase signaling pathways is frequently associated with various human diseases, including cancer. In this study, pathogenic mutations in human protein kinase domains were mapped and categorized based on their relevance to disease type. It was found that cancer-associated mutations primarily occurred within the catalytic and activation loops of the kinase domain, while non-cancer-related mutations were mainly located outside of these regions. Additionally, a previously unexplored hotspot at residue R371 of the AURKA structure was identified, which harbored a high number of exclusively non-cancer-related pathogenic mutations (21).
Article
Chemistry, Physical
Christos Lamprakis, Ioannis Andreadelis, John Manchester, Camilo Velez-Vega, Jose S. Duca, Zoe Cournia
Summary: The study suggests that Martini 2.2P overestimates the free energy of association for proteins, while Martini 3 performs better in describing the association of membrane proteins. Near-native dimer complexes are identified as minima in the free energy surface, although not always as the lowest minima.
JOURNAL OF CHEMICAL THEORY AND COMPUTATION
(2021)