Article
Endocrinology & Metabolism
David A. Salisbury, David Casero, Zhengyi Zhang, Dan Wang, Jason Kim, Xiaohui Wu, Laurent Vergnes, Aashiq H. Mirza, Paola Leon-Mimila, Kevin J. Williams, Adriana Huertas-Vazquez, Samie R. Jaffrey, Karen Reue, Jianjun Chen, Tamer Sallam
Summary: Salisbury et al. demonstrate that m(6)A modifications play a sex-dependent and dietary-dependent role in regulating hepatic lipid metabolism, triaging lipogenic transcripts for degradation and preventing hepatic triglyceride accumulation. The loss of m(6)A control in male livers under lipid-rich conditions leads to a more 'feminized' hepatic lipid composition, which can be significantly diminished by liver-specific deletion of the m(6)A complex protein Mettl14 in both male and female mice. Additionally, the m(6)A installing machinery is subject to transcriptional control by the sex-responsive BCL6-STAT5 axis in response to dietary conditions, providing insights into the molecular basis for sex-specific differences in hepatic lipid traits.
Article
Biochemistry & Molecular Biology
Akiko Yamaji-Hasegawa, Motohide Murate, Takehiko Inaba, Naoshi Dohmae, Masayuki Sato, Fumihiro Fujimori, Yasushi Sako, Peter Greimel, Toshihide Kobayashi
Summary: We have identified a mushroom-derived protein, maistero-2, that specifically binds to cholesterol and can label cholesterol in cells with higher sensitivity than existing probes. Through our study, we have revealed the changes and distribution of cholesterol during neurite outgrowth.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2022)
Review
Biochemistry & Molecular Biology
Jie Yu, David D. Boehr
Summary: Re-localization of enzymes is crucial for their catalytic activity and cell signaling. Recent studies have uncovered the mechanisms by which enzymes interact with lipid membranes and how this interaction regulates protein structure and function.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2023)
Article
Cell Biology
Yeongho Kim, Grace Mavodza, Can E. Senkal, Christopher G. Burd
Summary: Homeostatic mechanisms maintain the lipid compositions of organelle membranes. Acute depletion of cholesterol results in increased synthesis of very long chain sphingolipids, which play a key role in maintaining plasma membrane cholesterol content and lipid order homeostasis. This study establishes the existence of a cholesterol-sphingolipid regulatory axis that maintains plasma membrane lipid homeostasis via regulation of sphingomyelin synthesis and trafficking.
JOURNAL OF CELL BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Laura Lemel, Katarzyna Niescierowicz, M. Dolores Garcia-Fernandez, Leonardo Darre, Thierry Durroux, Marta Busnelli, Mylene Pezet, Fabrice Rebeille, Juliette Jouhet, Bernard Mouillac, Carmen Domene, Bice Chini, Vadim Cherezov, Christophe J. Moreau
Summary: The study revealed a stable binding of cholesterol molecules to OXTR in the presence of orthosteric ligands, leading to a positive cross-regulation between cholesterol and orthosteric ligands, which preserves the activity of the receptor in cholesterol-depleted membranes.
JOURNAL OF LIPID RESEARCH
(2021)
Article
Food Science & Technology
Chontida Tangsongcharoen, Jose L. Toca-Herrera, Boonhiang Promdonkoy, Sudarat Tharad
Summary: This study investigated the importance of the conserved T144 residue in the alpha D-beta 4 loop of Cyt2Aa2 protein for lipid binding on fluid lipid membranes. The results showed that replacing threonine with alanine hinders the binding of Cyt2Aa2 on liquid lipid membranes, providing a possibility to modify the protein to specific cells via lipid phase selection.
Article
Engineering, Biomedical
Xiaozhao Wang, Cai Yao, Xudong Yao, Junxin Lin, Rui Li, Kun Huang, Weiming Lin, Xiaojun Long, Chao Dai, Jiajun Dong, Xuegong Yu, Wenwen Huang, Wenjian Weng, Qi Wang, Hongwei Ouyang, Kui Cheng
Summary: In this study, a light-activated molecular switch was developed on graphene/silicon substrates to regulate cell attachment/detachment behaviors. The conformational changes of ECM proteins stimulated by light illumination resulted in reduced specificity of cell surface receptor-ligand interaction, leading to dynamic regulation of cell adhesion and detachment.
BIOACTIVE MATERIALS
(2023)
Article
Physics, Multidisciplinary
Taras Sych, Ramin Omidvar, Rafael Ostmann, Thomas Schubert, Annette Brandel, Ludovic Richert, Yves Mely, Josef Madl, Winfried Roemer
Summary: The dynamic reorganization of lipid rafts is important in host cell infection by human pathogens. Bacteria induce this reorganization through interactions with glycosphingolipids (GSLs). The authors studied how the bacterial lectin LecA affects the nanometric organization of membranes and found that it causes dispersion of liquid-ordered domains and surface deformation, providing insights into P. aeruginosa infection.
COMMUNICATIONS PHYSICS
(2023)
Article
Cell Biology
Troy A. Kervin, Michael Overduin
Summary: The recognition of phosphatidylinositol phosphates (PIPs) by proteins plays a crucial role in cellular processes, with phosphorylation modification being a key regulatory mechanism. Analysis of protein structures and phosphoproteomic databases reveals that the regulation of membrane readers is essential for selective protein targeting to organelles.
Article
Biochemistry & Molecular Biology
Seul Hoo Lee, Hogyun Seo, Hwaseok Hong, Mijeong Kim, Kyung-Jin Kim
Summary: Researchers found that IsTBP in Ideonella sakaiensis has high specificity and affinity for TPA, which helps in the degradation of PET plastic. They also developed an IsTBP variant with enhanced sensitivity, which can be used as a biosensor for PET degradation.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2023)
Article
Chemistry, Multidisciplinary
Hwankyu Lee
Summary: All-atom molecular dynamics simulations were conducted on 10 nm-sized anionic polystyrene (PS) particles complexed with plasma proteins and adsorbed onto lipid bilayers. The simulations revealed that proteins bound more weakly to the zwitterionic leaflet and more strongly to the anionic leaflet due to charge interactions. Additionally, interactions between proteins and the anionic leaflet disrupted protein helical structure and lipid organization, increasing the lateral dynamics of the bilayers.
Article
Multidisciplinary Sciences
Iven Winkelmann, Povilas Uzdavinys, Ian M. Kenney, Joseph Brock, Pascal F. Meier, Lina-Marie Wagner, Florian Gabriel, Sukkyeong Jung, Rei Matsuoka, Christoph von Ballmoos, Oliver Beckstein, David Drew
Summary: The study focuses on the mechanism of Na+/H+ exchange in cell homeostasis using the Na+/H+ antiporter NhaA as a model. The researchers discovered that a pH-sensitive switch on the cytoplasmic surface, called the pH sensor, controls the accessibility of substrates to the ion-binding site. The crystal structure of NhaA at active pH 6.5 revealed the rearrangement of residues in the pH sensor, forming new interactions that widen the inward-facing cavity, allowing water and Na+ to access the ion-binding site.
NATURE COMMUNICATIONS
(2022)
Article
Multidisciplinary Sciences
Radda Rusinova, Changhao He, Olaf S. Andersen
Summary: This study suggests that drugs can regulate membrane protein function by altering bilayer properties, involving both direct interactions with the protein and subtle mechanisms through changes in bilayer properties that impact protein conformation. Drug-induced regulation of membrane protein function involves a complex interplay of mechanisms, including both direct binding and bilayer-mediated effects.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Chemistry, Multidisciplinary
Layara Akemi Abiko, Raphael Dias Teixeira, Sylvain Engilberge, Anne Grahl, Tobias Muhlethaler, Timothy Sharpe, Stephan Grzesiek
Summary: Recent high-pressure NMR results suggest that the beta(1)-adrenergic receptor (beta,AR) has empty cavities in its preactive conformation, which disappear in the active conformation. This study identified and analyzed these cavities using X-ray crystallography and found that one cavity is in direct contact with the cholesterol-binding pocket. Solution NMR experiments further confirmed that a cholesterol analogue impedes the formation of the active conformation of beta(1)AR, leading to reduced affinity between isoprenaline, G protein-mimicking nanobody Nb80, and beta(1)AR. The findings explain the negative allosteric modulatory function of cholesterol on beta(1)AR and may contribute to the development of allosteric drugs.
Review
Cell Biology
Hossein Roghani-Shahraki, Mohammad Karimian, Saboora Valipour, Mohaddeseh Behjati, Reza Arefnezhad, Abolfazl Mousavi
Summary: Impaired lipid profile is closely related to the development and mortality of diseases. Herbal therapy is considered a promising approach for the treatment of these disorders, with some herbal compounds showing beneficial effects on lipid profile abnormalities.
JOURNAL OF CELLULAR PHYSIOLOGY
(2021)
Review
Genetics & Heredity
Arun Radhakrishnan, Gowthamarajan Kuppusamy, Sivasankaran Ponnusankar, Nikhitha K. Shanmukhan
PHARMACOGENOMICS JOURNAL
(2020)
Article
Cell Biology
Xiaobo Wang, Bishuang Cai, Xiaoming Yang, Oluwatoni O. Sonubi, Ze Zheng, Rajasekhar Ramakrishnan, Hongxue Shi, Luca Valenti, Utpal B. Pajvani, Jaspreet Sandhu, Rodney E. Infante, Arun Radhakrishnan, Douglas F. Covey, Kun-Liang Guan, Jochen Buck, Lonny R. Levin, Peter Tontonoz, Robert F. Schwabe, Ira Tabas
Editorial Material
Biochemistry & Molecular Biology
Kristen A. Johnson, Arun Radhakrishnan
JOURNAL OF LIPID RESEARCH
(2020)
Article
Microbiology
Michael E. Abrams, Kristen A. Johnson, Sofya S. Perelman, Li-shu Zhang, Shreya Endapally, Katrina B. Mar, Bonne M. Thompson, Jeffrey G. McDonald, John W. Schoggins, Arun Radhakrishnan, Neal M. Alto
NATURE MICROBIOLOGY
(2020)
Editorial Material
Biochemistry & Molecular Biology
Michael E. Abrams, Kristen A. Johnson, Arun Radhakrishnan, Neal M. Alto
JOURNAL OF LIPID RESEARCH
(2020)
Article
Biochemistry & Molecular Biology
Arun Radhakrishnan, Rajat Rohatgi, Christian Siebold
NATURE CHEMICAL BIOLOGY
(2020)
Article
Biochemistry & Molecular Biology
Daniel L. Kober, Arun Radhakrishnan, Joseph L. Goldstein, Michael S. Brown, Lindsay D. Clark, Xiao-chen Bai, Daniel M. Rosenbaum
Summary: Cholesterol-sensing protein Scap regulates the transport of sterol regulatory element-binding proteins (SREBPs) from the endoplasmic reticulum to the Golgi apparatus, with cholesterol inhibiting Scap transport by binding to L1 and subsequently binding to Insig to inhibit cholesterol synthesis.
Review
Biochemistry & Molecular Biology
Arun Radhakrishnan, Gowthamarajan Kuppusamy
Summary: Personalized medicine aims to individualize drug therapy for maximum benefit without adverse reactions. Genetic polymorphism is a crucial factor contributing to inter-individual variability, with dose titration being the current standard practice. Technological advancements have made converting genotypic data into optimized doses easier, but challenges remain in successfully finding individualized doses for many drugs, leading to a trial and error approach. Technologies like smart drug delivery systems hold potential for advancing personalized medicine beyond dose titration towards next-generation personalized therapy.
CURRENT DRUG METABOLISM
(2021)
Review
Pharmacology & Pharmacy
Arun Radhakrishnan, Gowthamarajan Kuppusamy, Sivasankaran Ponnusankar, Srinivas Mutalik
Summary: Personalized medicine allows for customized drug therapy to maximize efficacy and avoid side effects. Genetic polymorphisms play a major role in interindividual variability. While converting genotypic data into an optimum dose has become easier, determining personalized doses for some medications can still be challenging. The pharmaceutical industry has advanced smart drug delivery methods that can further enhance personalized medicine.
Article
Biology
Maia Kinnebrew, Giovanni Luchetti, Ria Sircar, Sara Frigui, Lucrezia Vittoria Viti, Tomoki Naito, Francis Beckert, Yasunori Saheki, Christian Siebold, Arun Radhakrishnan, Rajat Rohatgi
Summary: The study reveals that PTCH1 inhibits the activity of Smoothened by depleting accessible cholesterol from the outer leaflet of the plasma membrane, potentially involving an exchange of potassium ions. This finding establishes a general framework for investigating how proteins change cholesterol accessibility to regulate membrane-dependent processes in cells.
Article
Biology
David B. Heisler, Kristen A. Johnson, Duo H. Ma, Maikke B. Ohlson, Lishu Zhang, Michelle Tran, Chase D. Corley, Michael E. Abrams, Jeffrey G. McDonald, John W. Schoggins, Neal M. Alto, Arun Radhakrishnan, Suzanne R. Pfeffer
Summary: Most cholesterol in animal cell plasma membranes is sequestered by phospholipids and transmembrane proteins, but when cholesterol concentration exceeds the membrane's capacity, a new pool of cholesterol called accessible cholesterol emerges. Transport of accessible cholesterol between the plasma membrane and endoplasmic reticulum (ER) is critical for maintaining cholesterol balance. Activation of acyl coenzyme A: cholesterol acyltransferase (ACAT) by the oxysterol 25-hydroxycholesterol (25HC) leads to depletion of accessible cholesterol from the plasma membrane, sustained through SREBP suppression and continued ACAT activation. This mechanism is involved in immune activities mediated by 25HC and related oxysterols.
Article
Pharmacology & Pharmacy
Pooja Sudarsan, Resia Varghese, Aneena Suresh, Arun Radhakrishnan
Summary: The mainstay treatment for phenytoin-induced paradoxical seizure and blood dyscrasias is to monitor the patient and dose titration, highlighting the challenges in dosing phenytoin for clinicians.
JOURNAL OF PHARMACY PRACTICE
(2021)
Article
Multidisciplinary Sciences
Daniel L. Kober, Shimeng Xu, Shili Li, Bilkish Bajaj, Guosheng Liang, Daniel M. Rosenbaum, Arun Radhakrishnan
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2020)
Review
Pharmacology & Pharmacy
Nirmala Nayak, Preethi Somanna, Amit B. Patil, Arun Radhakrishnan
THERAPEUTIC DELIVERY
(2020)
Article
Pharmacology & Pharmacy
Sumathi Rajamani, Tamizharasi Sengodan, Sivakumar Thangavelu, Nikhitha K. Shanmukhan, Arun Radhakrishnan
INDONESIAN JOURNAL OF PHARMACY
(2019)