Article
Biology
Lise M. Sjogaard-Frich, Andreas Prestel, Emilie S. Pedersen, Marc Severin, Kristian Kolby Kristensen, Johan G. Olsen, Birthe B. Kragelund, Stine Falsig Pedersen
Summary: Through various biophysical techniques, this study reveals the complex interaction mechanism between CaM and NHE1, identifying multiple states and structures of the NHE1:CaM complex that can be modulated by stoichiometries, calcium concentrations, and phosphorylation. Experimental results suggest that CaM may enhance NHE1 regulation and indicate that this structural diversity is relevant to other CaM complexes as well.
Article
Multidisciplinary Sciences
Yanli Dong, Yiwei Gao, Alina Ilie, DuSik Kim, Annie Boucher, Bin Li, Xuejun C. Zhang, John Orlowski, Yan Zhao
Summary: NHE1 and CHP1 are proteins that regulate intracellular pH and volume homeostasis. The structures of the human NHE1-CHP1 complex provide insight into how CHP1 influences the pH-sensitivity of NHE1 and interactions with NHE1 inhibitors.
NATURE COMMUNICATIONS
(2021)
Article
Biochemistry & Molecular Biology
Xiuju Li, Benjamin Buckley, Konstantin Stoletov, Yang Jing, Marie Ranson, John D. Lewis, Mike Kelso, Larry Fliegel
Summary: This study examined the role of NHE1 and uPA in prostate cancer cell migration and colony formation, finding that only uPA activity played a critical role in cell migration and colony formation, while the effect of NHE1 was minor.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Physiology
Mallorie Poet, Denis Doyen, Emmanuel Van Obberghen, Gisele Jarretou, Yann Bouret, Laurent Counillon
Summary: Na+/H+ exchangers are membrane transporters that are present in all living systems and play a crucial role in regulating cellular pH and volume. The recent revelation of their molecular structures using Cryo-EM has provided valuable insights into their mechanisms and regulation.
FRONTIERS IN PHYSIOLOGY
(2022)
Article
Microbiology
Joao Paulo Ferreira Rodrigues, Leonardo Loch, Thiago Souza Onofre, Nobuko Yoshida
Summary: The involvement of NHE1 in the internalization of Trypanosoma cruzi metacyclic trypomastigotes was studied. NHE1 plays a role in maintaining the activation status of diverse protein kinases and preventing inappropriate F-actin arrangement, thus affecting lysosome distribution.
Article
Biochemistry & Molecular Biology
Xiuju Li, Justin Kim, Jing Yang, Debajyoti Dutta, Larry Fliegel
Summary: Mutations in amino acids within two modeled inhibitor binding sites of human NHE1 were studied, revealing changes in sensitivity to inhibitor EMD87580 in certain mutants.
BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES
(2021)
Article
Biochemistry & Molecular Biology
Li Shao, Tong Xu, Xiutao Zheng, Dandan Shao, Haitao Zhang, Huiwen Chen, Zhenglai Zhang, Mingxue Yan, Heba Abdel-Motaal, Juquan Jiang
Summary: This study reports a novel Na+/H+ antiporter NhaM and its homologs constitute a NhaM family, suggesting the vital role of oligomerization in the function of these antiporters.
JOURNAL OF MOLECULAR BIOLOGY
(2021)
Article
Cell Biology
Xiuju Li, Larry Fliegel
Summary: In breast cancer, pH regulatory proteins and the tumor microenvironment play a crucial role in cancer cell metastasis. This study found that the acid-extruding protein NHE1 has an important role in the migration and invasion of basal-like triple-negative breast cancer cells.
MOLECULAR AND CELLULAR BIOCHEMISTRY
(2022)
Article
Multidisciplinary Sciences
Marianna Dionisi, Beatrice Riva, Marta Delconti, Cristina Meregalli, Alessia Chiorazzi, Annalisa Canta, Paola Alberti, Valentina Carozzi, Eleonora Pozzi, Dmtry Lim, Armando A. A. Genazzani, Carla Distasi, Guido Cavaletti
Summary: Oxaliplatin (OHP)-induced peripheral neurotoxicity (OIPN) is a dose-limiting side effect of colorectal cancer treatment. OHP affects intracellular pH homeostasis in dorsal root ganglion (DRG) neurons by inhibiting Na+/H+ exchanger isoform-1 (NHE1) activity. The inhibition of NHE1 by OHP is sensitive to calcineurin (CaN) inhibition. These findings suggest new mechanisms of OHP-induced neurotoxicity and potential targets for therapeutic intervention.
SCIENTIFIC REPORTS
(2023)
Article
Chemistry, Multidisciplinary
Salvatore Galati, Dimitar Yonchev, Raquel Rodriguez-Perez, Martin Vogt, Tiziano Tuccinardi, Juergen Bajorath
Summary: This study successfully predicted selective inhibitors for human hCA IX and identified key compound features. By combining machine learning and analysis of X-ray structures, the models have considerable potential to aid in the identification of new hCA IX-selective compounds.
Article
Cell Biology
Larry Fliegel
Summary: NHE1 is a plasma membrane protein present in human cells, playing a crucial role in regulating intracellular pH and being involved in heart disease and cancer metastasis. Mutations in the NHE1 gene can lead to various severe defects and diseases, affecting neuronal degeneration, growth, and reproductive ability. Genetic polymorphisms in NHE1 may significantly alter its function, leading to diverse human phenotypes and involvement in disease.
MOLECULAR AND CELLULAR BIOCHEMISTRY
(2021)
Review
Cardiac & Cardiovascular Systems
Morris Karmazyn, Grant N. Pierce, Larry Fliegel
Summary: The mammalian Na+/H+ exchanger (NHE) is a ubiquitous membrane protein family in humans that regulates intracellular pH. NHE1, one of its isoforms, is present on the plasma membrane and plays a role in cardiovascular diseases. Inhibitors of NHE1 have shown excellent cardioprotection in experimental studies, but clinical trial results have been mixed. Further development of novel compounds that inhibit NHE1, with different structures from previous drugs, may lead to promising treatments for cardiovascular diseases.
REVIEWS IN CARDIOVASCULAR MEDICINE
(2022)
Article
Pharmacology & Pharmacy
Yixiang Xu, Chao Zhang, Kai Jiang, Xinchun Yang, Feng Chen, Zhiyang Cheng, Jinlong Zhao, Jiaxing Cheng, Xiaokang Li, Xin Chen, Luoyifan Zhou, Hao Duan, Yunyuan Huang, Yaozu Xiang, Jian Li
Summary: To address the issue of separating ant-heart failure (HF) activity from glucose-lowering side-effects, the researchers conducted structural repurposing of the SGLT2 inhibitor EMPA. The optimized derivative JX01 showed weaker SGLT2-inhibitory activity and lower glucose-lowering side-effects, but better NHE1-inhibitory activity and HF mice cardioprotective effect. Furthermore, JX01 demonstrated good safety profiles and pharmacokinetic properties. This study provides a paradigm for discovering novel anti-HF drugs and indirectly highlights the importance of SGLT2-independent molecular mechanisms in the cardioprotective effects of SGLT2 inhibitors.
ACTA PHARMACEUTICA SINICA B
(2023)
Article
Andrology
Qian Hu, Jiali Hu, Cuiyu Chen, Yang Wang, Yu Zhang, Jielin Wan, Ouyang Jing, Hanying Yi, Shiyu Wang, Weihua Huang, Jie Liu, Wei Zhang, Howard L. McLeod, Ran Xu, Yijing He
Summary: The study found that propranolol can inhibit the growth of bladder cancer cells and induce apoptosis. It also inhibits bladder cancer growth in a mouse model. Propranolol also activates systemic antitumor immune response.
TRANSLATIONAL ANDROLOGY AND UROLOGY
(2022)
Article
Biochemistry & Molecular Biology
Ornella Cuomo, Rossana Sirabella, Francesca Boscia, Antonella Casamassa, Jonathan Lytton, Lucio Annunziato, Giuseppe Pignataro
Summary: NCKX2 plays a crucial role in the neuroprotective effect of ischemic preconditioning and its expression is regulated through the p-AKT pathway. Knocking out NCKX2 significantly prevents the protective effect of ischemic preconditioning.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Biochemistry & Molecular Biology
Tran Thanh Tam Pham, Jan K. Rainey
Summary: Nuclear magnetic resonance (NMR) spectroscopy is used to determine atomic-level information on intermolecular interactions, molecular structure, and molecular dynamics in the cellular environment, with a focus on both intracellular and cell surface studies. Particularly, NMR techniques applied for on-cell studies can provide important insights into ligand interactions with cell surface membrane proteins and other cell surface molecules.
BIOCHEMISTRY AND CELL BIOLOGY
(2021)
Article
Cell Biology
Shobha Dagamajalu, D. A. B. Rex, Pushparani Devi Philem, Jan K. Rainey, T. S. Keshava Prasad
Summary: The apelin receptor (APLNR) is a widely distributed G-protein coupled receptor in the human body that regulates various physiological effects. The network map of APLNR signaling pathway has been curated to provide a reference for further research on this receptor system.
JOURNAL OF CELL COMMUNICATION AND SIGNALING
(2022)
Article
Cell Biology
Shobha Dagamajalu, D. A. B. Rex, G. P. Suchitha, Akhila B. Rai, Jan K. Rainey, T. S. Keshava Prasad
Summary: Elabela, a recently discovered ligand, plays crucial roles in diverse biological processes such as embryonic cardiovascular development and kidney protection by activating signaling pathways through APLNR.
JOURNAL OF CELL COMMUNICATION AND SIGNALING
(2022)
Article
Biophysics
Qinyan Song, Xiang-Qin Liu, Jan K. Rainey
Summary: The human MDMX protein, also known as MDM4, plays a crucial role in regulating the activity of the tumor suppressor protein p53. It inhibits p53 transcriptional activity and promotes its degradation by stimulating the E3 ubiquitin ligase activity of MDM2. Overexpression of MDMX is associated with various forms of cancer. This study used NMR spectroscopy to investigate the structure and function of the acidic domain of MDMX. The results showed that this region is intrinsically disordered with localized variation in inferred secondary structure propensity.
BIOMOLECULAR NMR ASSIGNMENTS
(2022)
Article
Hematology
Vinothkumar Rajan, Sergey Prykhozhji, Aditya Pandey, Alejandro M. Cohen, Jan K. Rainey, Jason N. Berman
Summary: This study identifies the significant role of the KIT D816V mutation in haematological malignancies and reveals its distinct activation mechanism compared to the wild type, suggesting new targets for therapeutic interventions.
BRITISH JOURNAL OF HAEMATOLOGY
(2023)
Article
Biophysics
Surendra Kumar Verma, Hessameddin Yaghoobi, Patrick Slaine, Samuel J. Baldwin, Jan K. Rainey, Laurent Kreplak, John P. Frampton
Summary: In this study, collagen fibers were successfully produced using a contact drawing method. The well-ordered collagen structures formed through contact drawing technology exhibited mechanical properties similar to native collagen fibers.
COLLOIDS AND SURFACES B-BIOINTERFACES
(2022)
Article
Chemistry, Multidisciplinary
Lizzy A. Baker, Lingling Xu, Farideh Badichi Akher, Madelaine K. Robertson, Lauren Pugsley-DeBruyn, Chloe Xiaoyi Ma, Xiang-Qin Liu, John P. Frampton, Jan K. Rainey
Summary: Spider silk, especially aciniform silk, has great potential as biomaterials due to their excellent mechanical properties and low immunogenicity. In this study, an engineered aciniform silk construct, N(B)Silk, fused with neurotrophic factor and nerve growth factor, is shown to form robust films that can support cell survival and promote neuronal differentiation and growth.
ADVANCED FUNCTIONAL MATERIALS
(2022)
Article
Biochemistry & Molecular Biology
Qinyan Song, Xiang-Qin Liu, Jan K. Rainey
Summary: The tumor suppressor protein p53 is regulated by negative regulators MDM2 and MDMX, with the AD of MDMX recently found to inhibit the p53-MDMX interaction. In this study, it is shown through NMR spectroscopy and ITC that the MDMX AD can directly interact with the MDM2 NTD, inhibiting the p53-MDM2 interaction and acting as a regulatory domain.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
(2022)
Article
Biophysics
Qinyan Song, Xiang-Qin Liu, Jan K. Rainey
Summary: The human MDM2 protein regulates the tumor suppressor protein p53 through multiple mechanisms, involving its N-terminal domain for binding to p53 and its central acidic domain for regulating p53 ubiquitination. The structural characteristics of the MDM2 acidic domain have been investigated using solution-state NMR spectroscopy, revealing that it behaves as a disordered protein.
BIOMOLECULAR NMR ASSIGNMENTS
(2023)
Article
Chemistry, Medicinal
Zachary B. Visser, Surendra Kumar Verma, Jan K. Rainey, John P. Frampton
Summary: This study presents a simple, cost-effective, and scalable method for dry spinning crosslinked PVA fibers for the development of polymeric drug releasing systems. The method utilizes entangled PVA solution to form liquid bridges that are drawn into rapidly drying fibers through extensional flow. By introducing glyoxal to the PVA solution, the fibers are crosslinked and can be loaded with quercetin. The glyoxal-crosslinked PVA fiber scaffolds retain their morphology and slowly degrade, releasing the loaded quercetin in a concentration-dependent manner. The released quercetin promotes the growth of PC12 cells on the fibers.
ACS PHARMACOLOGY & TRANSLATIONAL SCIENCE
(2022)
Article
Biochemistry & Molecular Biology
Jeffrey R. Simmons, Genevieve Gasmi-Seabrook, Jan K. Rainey
Summary: Orb-weaving spiders produce multiple types of silk with distinct biological roles, protein compositions, and mechanics. In this study, the researchers characterized the core repetitive domain of Argiope argentata PySp1, which is composed of the pyriform spidroin 1 (PySp1). They used NMR spectroscopy to analyze its structure and found a structured core surrounded by disordered tails. The study also revealed the modularity of the Py unit in the repetitive domain.
BIOCHEMISTRY AND CELL BIOLOGY
(2023)
Article
Multidisciplinary Sciences
Pawan Kumar, Azadeh Kermanshahi-pour, Satinder Kaur Brar, Chunbao Charles Xu, Quan Sophia He, Sara Evans, Jan K. Rainey
Summary: This study investigated the impact of different pretreatment methods on the enzymatic digestibility of wood and found that acetosolv pulping-alkaline hydrogen peroxide bleaching was the most effective pretreatment. In addition, the optimized enzyme cocktail showed higher yield than individual enzymes and the scCO(2) pretreatment had negligible effect on the structure and activity of the enzyme cocktail.
Article
Chemistry, Medicinal
Zachary B. Visser, Surendra Kumar Verma, Jan K. Rainey, John P. Frampton
Summary: In this study, a simple and cost-effective method for producing crosslinked PVA fibers is presented. The crosslinking conditions were optimized to achieve desired fiber morphology and drug release properties. The results demonstrate the potential of these fibers as drug delivery scaffolds.
ACS PHARMACOLOGY & TRANSLATIONAL SCIENCE
(2022)
Article
Materials Science, Biomaterials
Nauman Nazeer, Jeffrey R. Simmons, Jan K. Rainey, Juan Carlos Rodriguez-Lecompte, Marya Ahmed
Summary: In this study, host defense protein-derived peptides self-assembled into DSNs nanospheres and were stabilized using beta-CD and fucoidan, enhancing antibacterial efficacy and physiological stability. Comparisons between beta-CD-DSNs and FC-DSNs showed that DSNs formed in the presence of beta-CD were highly stable, exhibited high cellular uptake, bacterial flocculation, and improved antibacterial effects in a range of bacteria.
JOURNAL OF MATERIALS CHEMISTRY B
(2021)
Meeting Abstract
Biophysics
Jeffrey R. Simmons, Genevieve Gasmi-Seabrook, Jan K. Rainey
BIOPHYSICAL JOURNAL
(2021)