Article
Chemistry, Multidisciplinary
Mark T. Agasid, Lars Sorensen, Leonhard H. Urner, Jun Yan, Carol Robinson
Summary: The use of mass spectrometry to study G protein-coupled receptors has revealed insights into sodium binding and ligand-induced changes, providing valuable information for understanding GPCR function.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2021)
Article
Biology
Sabab Hasan Khan, Sean M. Braet, Stephen John Koehler, Elizabeth Elacqua, Ganesh Srinivasan Anand, C. Denise Okafor
Summary: This study investigates ligand-induced conformational changes in a reconstructed ancestral nuclear receptor and generates receptor variants with altered ligand specificities. Cellular and biophysical experiments, as well as atomistic molecular dynamics simulations, are used to characterize these conformational changes and understand their impact on ligand responses.
Article
Biochemistry & Molecular Biology
Wonjo Jang, Sumin Lu, Xin Xu, Guangyu Wu, Nevin A. Lambert
Summary: By studying G protein variants that can form GPCR-G protein complexes without nucleotide release, it was found that selectivity is reduced and most GPCRs interact with most variants. These findings suggest the absence of absolute structural incompatibility between noncognate receptor-G protein pairs and support the role of transient intermediate states in coupling selectivity.
NATURE CHEMICAL BIOLOGY
(2023)
Review
Endocrinology & Metabolism
Fanhua Wang, Mingyao Liu, Ning Wang, Jian Luo
Summary: This review discusses the role of G-protein coupled receptors (GPCRs) in osteoarthritis (OA), including the pathophysiological processes involved, preclinical and clinical trial data, and the challenges in developing therapies targeting GPCRs for OA.
FRONTIERS IN ENDOCRINOLOGY
(2022)
Review
Cardiac & Cardiovascular Systems
Yuanqiang Li, Boyu Li, Wei-Dong Chen, Yan-Dong Wang
Summary: Cardiovascular diseases (CVDs) are the leading cause of death globally, accounting for nearly 30% of deaths worldwide annually. G-protein-coupled receptors (GPCRs) are vital in regulating cellular physiology and pathology, and play a crucial role in CVDs. Targeting GPCRs has become an important approach for the treatment of CVDs, with some GPCR antagonists serving as standard therapy.
FRONTIERS IN CARDIOVASCULAR MEDICINE
(2023)
Review
Biochemistry & Molecular Biology
Wen-Yi Tseng, Martin Stacey, Hsi-Hsien Lin
Summary: Disorders of the immune system have a significant impact on health, and cell surface receptors play a critical role in immune responses. Selective members of the aGPCR family are expressed in different immune cell types and have been implicated in immune dysfunctions and disorders due to their dual cell adhesion and signaling roles.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Chemistry, Physical
Lev Levintov, Harish Vashisth
Summary: RNA molecules, including viral RNA like TAR RNA from HIV-1, undergo conformational changes in response to environmental stimuli. When TAR RNA binds to ligands, its structure becomes significantly more stable with reduced fluctuations in helices. Unliganded TAR structures exhibit conformational dynamics that lead to the formation of binding pockets for ligands.
PHYSICAL CHEMISTRY CHEMICAL PHYSICS
(2021)
Review
Endocrinology & Metabolism
Joanna Filipowska, Nagesha G. Kondegowda, Nancy Leon-Rivera, Sangeeta Dhawan, Rupangi C. Vasavada
Summary: LGR4 is a marker for intestinal crypt stem cells that binds R-spondins/Norrin and plays a crucial role in the enhancement of Wnt signaling. In addition to its role in development, LGR4 has been found to participate in the regulation of TGF beta and NF kappa B signaling, act as an alternative receptor for RANKL in bone cells, trigger anti-inflammatory responses in various tissues, regulate circadian rhythm, adipogenesis, and energy expenditure.
FRONTIERS IN ENDOCRINOLOGY
(2022)
Article
Biology
Ramon Cierco Jimenez, Nil Casajuana-Martin, Adrian Garcia-Recio, Lidia Alcantara, Leonardo Pardo, Mercedes Campillo, Angel Gonzalez
Summary: The study analyzed 119,069 natural variants in human olfactory receptors, revealing a significant diversity of natural variations in the olfactory gene repertoire between individuals and populations, with a considerable number of changes occurring at the structurally conserved regions. Mutations in positions linked to the conserved GPCR activation mechanism were highlighted, which could imply phenotypic variation in olfactory perception.
Review
Biochemistry & Molecular Biology
Krzysztof Jozwiak, Anita Plazinska
Summary: Studies on different receptors belonging to class A of GPCRs reveal specific molecular mechanisms behind ligand directed signaling, including the role of important residues, the impact of ligand structural features on signaling, and the key interactions between ligands and receptors.
Review
Biochemistry & Molecular Biology
Dekel David, Ziv Bentulila, Merav Tauber, Yair Ben-Chaim
Summary: GPCRs are involved in signal transduction processes, and although they span the cell membrane, they have not been considered to be regulated by membrane potential. Recent studies, however, have shown that several GPCRs are voltage regulated. This review discusses the advances in understanding the voltage dependence of GPCRs, the suggested molecular mechanisms, and the possible physiological roles.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Pharmacology & Pharmacy
Kate F. Byrne, Ajay Pal, James F. Curtin, John C. Stephens, Gemma K. Kinsella
Summary: The focus of the review is on G-protein-coupled receptor (GPCR) targets, with chemokine, cannabinoid, and dopamine receptors showing promise. Further research is needed on potential targets such as MC4R, adhesion receptors, LPA, and Smo receptors to develop new drug-screening strategies for safe and effective GBM therapies.
DRUG DISCOVERY TODAY
(2021)
Article
Biochemistry & Molecular Biology
Damiano Clementel, Alessio Del Conte, Alexander Miguel Monzon, Giorgia F. Camagni, Giovanni Minervini, Damiano Piovesan, Silvio C. E. Tosatto
Summary: Residue interaction networks (RINs) have been proven effective in analyzing complex systems as an alternative to coordinate data. The new RING 3.0 version extends the previous functionality by supporting mmCIF format, providing typed interactions for the entire PDB chemical component dictionary, and employing probabilistic graphs for analyzing structural data. The web interface has also been expanded to enhance visualization and interactivity.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Wojciech Pietrus, Rafal Kurczab, Dagmar Stumpfe, Andrzej J. Bojarski, Juergen Bajorath
Summary: The study showed that introducing fluorine can significantly increase ligand potency, but the effect of fluorination on affinity varies depending on the fluorination position. Fluorination of the aromatic ring at the ortho position is favorable for potency enhancement, while fluorination of aliphatic fragments more often leads to a decrease in biological activity.
Article
Chemistry, Multidisciplinary
Yunfang Xiong, Ran Ke, Qingyu Zhang, Wenjun Lan, Wanjun Yuan, Karol Nga Ieng Chan, Tom Roussel, Yifan Jiang, Jing Wu, Shuai Liu, Alice Sze Tsai Wong, Joong Sup Shim, Xuanjun Zhang, Ruiyu Xie, Nelson Dusetti, Juan Iovanna, Nagy Habib, Ling Peng, Leo Tsz On Lee
Summary: This study reports the effective modulation of a GPCR for cancer treatment using small activating RNAs (saRNAs) for the first time. The saRNAs promote the expression of MAS1, a GPCR that counteracts cancer cell proliferation and migration. By enhancing MAS1 expression, these saRNAs suppress tumorigenesis and inhibit tumor progression in multiple cancer models. This research not only provides a new strategy for cancer therapy by targeting the renin-angiotensin system, but also offers a new avenue to modulate GPCR signaling through RNA activation.
Article
Chemistry, Medicinal
Christofer S. Tautermann, Florian Binder, Frank H. Buettner, Christian Eickmeier, Dennis Fiegen, Ulrike Gross, Marc A. Grundl, Ralf Heilker, Scott Hobson, Stefan Hoerer, Andreas Luippold, Volker Mack, Florian Montel, Stefan Peters, Supriyo Bhattacharya, Nagarajan Vaidehi, Gisela Schnapp, Sven Thamm, Markus Zeeb
JOURNAL OF MEDICINAL CHEMISTRY
(2019)
Review
Chemistry, Multidisciplinary
Michiel J. M. Niesen, Matthew H. Zimmer, Thomas F. Miller
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2020)
Article
Chemistry, Physical
Marco Pezzella, Krystel El Hage, Michiel J. M. Niesen, Sucheol Shin, Adam P. Willard, Markus Meuwly, Martin Karplus
JOURNAL OF PHYSICAL CHEMISTRY B
(2020)
Article
Biology
Martin D. Gelenter, Venkata S. Mandala, Michiel J. M. Niesen, Dina A. Sharon, Aurelio J. Dregni, Adam P. Willard, Mei Hong
Summary: By using solid-state NMR spectroscopy and molecular dynamics simulations, researchers found that water molecules in the channel of the influenza B M2 protein exhibit faster dynamics and higher orientational order in the open state compared to the closed state, establishing the necessary water network structure for proton hopping.
COMMUNICATIONS BIOLOGY
(2021)
Article
Biophysics
Matthew H. Zimmer, Michiel J. M. Niesen, Thomas F. Miller
Summary: Force-sensitive arrest peptides stall protein biosynthesis by inhibiting the ribosome, and can be restarted by a pulling force. Essential amino acids far from the peptidyl transferase center play a key role in responding to applied force. The mechanism of force-induced restart in relation to these amino acids remains unknown.
BIOPHYSICAL JOURNAL
(2021)
Article
Biochemistry & Molecular Biology
Rohit Suratekar, Pritha Ghosh, Michiel J. M. Niesen, Gregory Donadio, Praveen Anand, Venky Soundararajan, A. J. Venkatakrishnan
Summary: The highly contagious Delta variant of SARS-CoV-2 has become a prevalent strain globally. This study provides a systematic analysis of mutations in all the SARS-CoV-2 proteins and identifies six highly prevalent missense mutations in the Delta variant's viral life cycle-associated proteins. The study also reveals that the Delta variant has a more diverse repertoire of mutations across countries compared to the previously dominant Alpha variant.
MOLECULAR SYSTEMS BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Arin Nam, Atish Mohanty, Supriyo Bhattacharya, Sourabh Kotnala, Srisairam Achuthan, Kishore Hari, Saumya Srivastava, Linlin Guo, Anusha Nathan, Rishov Chatterjee, Maneesh Jain, Mohd W. Nasser, Surinder Kumar Batra, Govindan Rangarajan, Erminia Massarelli, Herbert Levine, Mohit Kumar Jolly, Prakash Kulkarni, Ravi Salgia
Summary: This study developed a mathematical approach based on game theory to model the response of non-small cell lung cancer cells to cisplatin treatment. The findings suggest that dynamic interactions and group behavior play a role in drug resistance, with tolerant cells displaying a 'persister-like' behavior and educating sensitive cells to evade chemotherapy. Furthermore, intermittent chemotherapy may be a better treatment strategy to reduce the emergence of tolerant cells in lung cancer.
Article
Medicine, General & Internal
Michiel J. M. Niesen, Colin Pawlowski, John C. O'Horo, Doug W. Challener, Eli Silvert, Greg Donadio, Patrick J. Lenehan, Abinash Virk, Melanie D. Swift, Leigh L. Speicher, Joel E. Gordon, Holly L. Geyer, John D. Halamka, A. J. Venkatakrishnan, Venky Soundararajan, Andrew D. Badley
Summary: This study evaluated the safety of the third dose of FDA-approved COVID-19 mRNA vaccines. The findings suggest that although the third dose is associated with an increased reporting of low-severity adverse events, the risk of severe adverse events remains comparable to the standard two-dose regime. This study provides evidence for the safety of third vaccination doses in eligible individuals for booster vaccination.
Article
Cell Biology
Praveen Anand, Patrick J. Lenehan, Michiel Niesen, Unice Yoo, Dhruti Patwardhan, Marcelo Montorzi, A. J. Venkatakrishnan, Venky Soundararajan
Summary: Acute cardiac injury has been observed in some COVID-19 patients, and it is hypothesized that molecular mimicry may trigger an autoimmune inflammatory reaction. This study investigates the presence of similar peptides in the SARS-CoV-2 proteome as those found in human heart proteins. The findings suggest that viral variants with peptides identical to human cardiac proteins should be further investigated for their role in cardiac inflammation.
CELL DEATH DISCOVERY
(2022)
Article
Medicine, General & Internal
Prakash Kulkarni, Atish Mohanty, Supriyo Bhattacharya, Sharad Singhal, Linlin Guo, Sravani Ramisetty, Tamara Mirzapoiazova, Bolot Mambetsariev, Sandeep Mittan, Jyoti Malhotra, Naveen Gupta, Pauline Kim, Razmig Babikian, Swapnil Rajurkar, Shanmuga Subbiah, Tingting Tan, Danny Nguyen, Amartej Merla, Sudarsan Kollimuttathuillam, Tanyanika Phillips, Peter Baik, Bradford Tan, Pankaj Vashi, Sagun Shrestha, Benjamin Leach, Ruchi Garg, Patricia L. Rich, F. Marc Stewart, Evan Pisick, Ravi Salgia
Summary: Drug resistance is a major obstacle in cancer treatment. However, the use of a 'Team Medicine' approach and the development of new therapeutic strategies, such as intermittent therapy, based on eco-evolutionary principles, have shown promising results. Incorporating these strategies into clinical protocols can enhance the precision of personalized medicine.
JOURNAL OF CLINICAL MEDICINE
(2022)
Article
Immunology
A. J. Venkatakrishnan, Praveen Anand, Patrick J. Lenehan, Rohit Suratekar, Bharathwaj Raghunathan, Michiel J. M. Niesen, Venky Soundararajan
Summary: The emergence of the heavily mutated Omicron variant of SARS-CoV-2 has raised global public health concerns. The Spike protein of Omicron carries 26 unique amino acid mutations. One of these mutations, ins214EPE, has not been observed in any other SARS-CoV-2 variant and may have been acquired through template switching. This template-switching event could involve other human coronaviruses that infect the same host cells as SARS-CoV-2 or a human transcript expressed in an Omicron-infected host cell.
Article
Medicine, General & Internal
Sravani Ramisetty, Prakash Kulkarni, Supriyo Bhattacharya, Arin Nam, Sharad S. Singhal, Linlin Guo, Tamara Mirzapoiazova, Bolot Mambetsariev, Sandeep Mittan, Jyoti Malhotra, Evan Pisick, Shanmuga Subbiah, Swapnil Rajurkar, Erminia Massarelli, Ravi Salgia, Atish Mohanty
Summary: Translational research in medicine involves collaboration between scientists from different disciplines to apply knowledge from basic sciences to clinical practice. This approach, known as 'Team Medicine', focuses on addressing specific medical goals through partnership between basic science researchers and clinicians. Using cisplatin resistance in non-small cell lung cancer (NSCLC) as an example, this study demonstrates how a 'Team Science' approach was used to identify a previously approved compound that can alleviate cisplatin resistance in NSCLC. It also highlights the potential of a 'Team Medicine' approach in understanding resistance mechanisms and developing strategies to overcome drug resistance in NSCLC.
JOURNAL OF CLINICAL MEDICINE
(2023)
Article
Medicine, Research & Experimental
Arjun Puranik, Patrick J. Lenehan, Eli Silvert, Michiel J. M. Niesen, Juan Corchado-Garcia, John C. O'Horo, Abinash Virk, Melanie D. Swift, Joel E. Gordon, Leigh Lewis Speicher, Holly L. Geyer, Walter Kremers, John Halamka, Andrew D. Badley, A. J. Venkatakrishnan, Venky Soundararajan
Summary: The mRNA-1273 and BNT162b2 vaccines provide strong protection against symptomatic SARS-CoV-2 infection. However, their effectiveness was reduced during July-September and mRNA-1273 had a lower risk of breakthrough infection compared to BNT162b2.
Article
Medicine, Research & Experimental
Colin Pawlowski, Patrick Lenehan, Arjun Puranik, Vineet Agarwal, A. J. Venkatakrishnan, Michiel J. M. Niesen, John C. O'Horo, Abinash Virk, Melanie D. Swift, Andrew D. Badley, John Halamka, Venky Soundararajan
Summary: The study analyzed the effectiveness of BNT162b2 and mRNA-1273 vaccines in preventing COVID-19 in a real-world setting, and found that both vaccines were highly effective in reducing SARS-CoV-2 infection rates and lowering the burden of COVID-19 on the healthcare system.
Meeting Abstract
Biotechnology & Applied Microbiology
Shirley Li, Maciej Kujawski, Lin Li, Harry Li, Supriyo Bhattacharya, Vaidehi Nagarajan, Paul Yazaki, Pamela J. Bjorkman, John Zaia, John E. Shively