Article
Biochemistry & Molecular Biology
Woori Ko, Byung-Chang Suh
Summary: The membrane phospholipid phosphatidylinositol 4,5-bisphosphate (PI(4,5)P-2) selectively modulates the gating of the TMEM16A(ac) channel in an agonistic manner, leading to the upregulation of TMEM16A(ac) functions in physiological conditions.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Luis Borges-Araujo, Marina E. Monteiro, Dalila Mil-Homens, Nuno Bernardes, Maria J. Sarmento, Ana Coutinho, Manuel Prieto, Fabio Fernandes
Summary: Despite its low abundance, PI(4,5)P-2 plays a key role in membrane-associated signaling events in eukaryotic cells. The presence of physiological divalent cations can affect the clustering of PI(4,5)P-2 and its interactions with proteins, which can have a significant impact on the organization and downstream interactions of PI(4,5)P-2-binding proteins in the plasma membrane. This study characterizes the effects of Ca2+ on the organization and protein-protein interactions of PI(4,5)P-2-binding proteins, providing insights into the complex regulation of PI(4,5)P-2 in cell signaling.
Review
Biochemistry & Molecular Biology
Yi Wen, Volker M. Vogt, Gerald W. Feigenson
Summary: Phosphatidylinositol 4,5-bisphosphate (PI(4,5)P-2) is a crucial component located at the inner leaflet of the cell membrane, constituting only 1-2% of total membrane lipids. Its synthesis and turnover are spatially and temporally regulated. Various factors, such as multivalent cations and cellular proteins interacting with PI(4,5)P-2, contribute to its versatile and dynamic distribution within membranes.
ANNUAL REVIEW OF BIOCHEMISTRY, VOL 90, 2021
(2021)
Review
Endocrinology & Metabolism
Stanko S. S. Stojilkovic, Tamas Balla
Summary: Plasma membrane and organelle membranes contain phosphoinositides that play important roles in cellular signaling and exocytosis. Three phosphoinositides, PI4P, PI(4,5)P2, and PI(3,4,5)P3, are particularly involved in hormone-producing pituitary cells. PI(4,5)P2 controls various pituitary cell functions, while also serving as a substrate for PI3-kinases to generate intracellular messengers PI(3,4,5)P3 and PI(3,4)P2. PI(4,5)P2 affects pituitary hormone release through ion channel gating, calcium signaling, and the exocytic pathway. PI4P is not only a precursor of PI(4,5)P2 but also a signaling molecule that regulates hormone secretion independently of PI(4,5)P2 in various cell types, including pituitary cells.
FRONTIERS IN ENDOCRINOLOGY
(2023)
Article
Cell Biology
Xinan Meng, Chandra Sugiarto Wijaya, Qingfang Shao, Suhong Xu
Summary: The Golgi apparatus accumulates at the wound site and facilitates membrane repair by converting PtdIns4P to PtdIns(4,5)P2 in response to plasma membrane damage in C. elegans. This finding advances our understanding of cellular survival mechanisms under mechanical stress.
JOURNAL OF CELL BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Kwon-Woo Kim, Byung-Chang Suh
Summary: Ethanol affects neuronal activity by reducing the open probability and PI(4,5)P-2 sensitivity of Kv7.2/7.3 channels in a cell type-specific manner, leading to an increase in membrane excitability in sympathetic neurons.
Article
Biochemistry & Molecular Biology
Maria J. Sarmento, Luis Borges-Araujo, Sandra N. Pinto, Nuno Bernardes, Joana C. Ricardo, Ana Coutinho, Manuel Prieto, Fabio Fernandes
Summary: PI(4,5)P-2 plays essential roles in cellular functions by dynamically organizing within the plasma membrane; in HeLa cells, it is compartmentalized without cholesterol dependence, and actin polymerization inhibition eliminates the compartmentalization.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Holly Dykstra, Cassi LaRose, Chelsea Fisk, Althea Waldhart, Xing Meng, Gongpu Zhao, Ning Wu
Summary: The interaction between GLUT1 and TXNIP in regulating cellular glucose uptake is essential and requires phosphatidylinositol 4,5-bisphosphate (PI(4,5)P-2 or PIP2).
BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES
(2021)
Article
Cell Biology
Archna Ravi, Lavinia Palamiuc, Brooke M. Emerling
Summary: While organelles are individual compartments with specialized functions, inter-organelle communication is essential for cellular homeostasis. This communication is mediated by phospholipids on organelle membranes, particularly phosphoinositides like phosphatidylinositol 4,5-bisphosphate (PI-4,5-P-2). This review focuses on the role of non-canonical Type II PIPKs in generating PI-4,5-P-2 and their impact on organelle crosstalk, cellular health, and human diseases.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Chemistry, Multidisciplinary
Joern Dietz, Marieelen Oelkers, Raphael Hubrich, Angel Perez-Lara, Reinhard Jahn, Claudia Steinem, Andreas Janshoff
Summary: A mechanism is proposed for full-length synaptotagmin-1 to interact with anionic bilayers and promote fusion in the presence of SNAREs. It is shown that the binding of synaptotagmin-1 to membranes depends on the presence and content of PI(4,5)P-2 in the absence of Ca2+. The interaction forces switch from weak to strong upon addition of Ca2+, leading to partial unfolding of the protein. Fusion of vesicles equipped with synaptotagmin-1 and synaptobrevin 2 with target membranes containing PS and PI(4,5)P-2 is accelerated in the presence of Ca2+, which is further enhanced by ATP.
Article
Chemistry, Medicinal
Lisbeth R. Kjolbye, Lars Sorensen, Jun Yan, Nils A. Berglund, Jesper Ferkinghoff-Borg, Carol V. Robinson, Birgit Schiott
Summary: This study used molecular dynamics simulations and native mass spectrometry to investigate the interaction between PI(4,5)P-2 lipids and GCGR, revealing differential affinities of the lipids to different conformations of GCGR. Furthermore, the study uncovered the role of a conserved binding site in stabilizing the inactive conformation of GCGR in class B GPCRs.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2022)
Article
Cell Biology
Alex G. Batrouni, Nirmalya Bag, Henry T. Phan, Barbara A. Baird, Jeremy M. Baskin
Summary: Phosphatidylinositol 4-kinase III alpha (PI4KIII alpha) is responsible for generating phosphatidylinositol (4)-phosphate at the plasma membrane, and the differential palmitoylation patterns of its anchor protein EFR3B control its distribution and phosphoinositide homeostasis.
JOURNAL OF CELL SCIENCE
(2022)
Article
Biochemistry & Molecular Biology
Chongxu Liu, Youjia Zhang, Liang Ge, Ling Li, Bo Wu, Junfeng Wang
Summary: STIMATE is an ER resident membrane protein that regulates calcium signaling and ER-PM junction maintenance by interacting with STIM1. It can interact with membranes containing specific lipid components, and its intrinsic disorder and specific amino acid sequences are essential for membrane binding.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2022)
Review
Biochemistry & Molecular Biology
Kuan Chen, Meng Zhang, Min Ye, Xue Qiao
Summary: This review summarizes 98 mutation sites in 25 plant OSCs and identifies conserved key residues through sequence alignment, while discussing structure-function relationships. Substrate selectivity is also summarized to probe the active site cavity of plant OSCs.
NATURAL PRODUCT REPORTS
(2021)
Article
Biochemistry & Molecular Biology
Nilesh Kumar, Bharat K. Mishra, Jinbao Liu, Binoop Mohan, Doni Thingujam, Karolina M. Pajerowska-Mukhtar, M. Shahid Mukhtar
Summary: Drought is a serious stressor in the environment that reduces plant growth and agricultural productivity. To understand its effects on plants, a systems biology approach was used to study the transcriptome of Arabidopsis during drought. Co-expression network analysis identified 117 transcription factors (TFs) with important properties. Mathematical modeling and simulations revealed major transcriptional events and the involvement of TFs. Experimental evidence validated the predictions, showcasing the potential of these TFs in crop engineering programs.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Eleonora Gianti, Simona Percec
Summary: This Perspective outlines recent progress and future directions for using machine learning in the design, synthesis, processing, and characterization of biomacromolecules. It highlights the importance of using machine learning to extract relevant information from chemistry and biology fields to advance our understanding of chemical and biomolecular systems.
Article
Biochemistry & Molecular Biology
Ravi Patel, Vincenzo Carnevale, Sudhir Kumar
Summary: Research has shown that negative selection between sites creates more invariant sites compared to site-specific preferences alone, with an increasing role over longer evolutionary periods. These findings highlight the mechanistic role of epistasis in site invariance and evolutionary rates.
MOLECULAR BIOLOGY AND EVOLUTION
(2022)
Article
Physiology
John Smith Del Rosario, Matthew Gabriel, Yevgen Yudin, Tibor Rohacs
Summary: TMEM120A is identified as a negative modulator of PIEZO2 channel activity, rather than a mechanically activated ion channel. Tmem120a expression decreases the amplitudes of PIEZO2 currents and increases the threshold of activation.
JOURNAL OF GENERAL PHYSIOLOGY
(2022)
Article
Biology
Deny Cabezas-Bratesco, Francisco A. Mcgee, Charlotte K. Colenso, Kattina Zavala, Daniele Granata, Vincenzo Carnevale, Juan C. Opazo, Sebastian E. Brauchi
Summary: Transient receptor potential (TRP) proteins are a diverse family of cation-selective channels, with detailed mechanisms of regulation still under debate. Through analysis, a highly conserved set of residues was discovered in TRP channels, positioned at equivalent locations in different subtypes, potentially influencing coupling strategies of various subgroups.
Article
Chemistry, Physical
Ruiyu Wang, Yunqian Zou, Richard C. Remsing, Naomi O. Ross, Michael L. Klein, Vincenzo Carnevale, Eric Borguet
Summary: Understanding the microscopic driving force of water wetting is challenging and important for material design. This study investigates the relations between structure, dynamics and hydrogen bonds of interfacial water on alumina surfaces using molecular dynamics simulations and experiments. The findings reveal superhydrophilicity of both surfaces, with the (0001) surface being more hydrophilic. The molecular dynamics simulations eliminate surface contamination and provide insights into the microscopic origin of the macroscopic superhydrophilicity: strong water-to-aluminol hydrogen bonds.
JOURNAL OF COLLOID AND INTERFACE SCIENCE
(2022)
Article
Chemistry, Multidisciplinary
Shaohua Zhang, Wei Li, Jiabin Luan, Abhinav Srivastava, Vincenzo Carnevale, Michael L. Klein, Jiawei Sun, Danni Wang, Serena P. Teora, Sjoerd J. Rijpkema, Johannes D. Meeldijk, Daniela A. Wilson
Summary: Researchers report an adaptive non-covalent binding strategy for surface functionalization using a hydrophobic anchor to insert into a poly(ethylene glycol) (PEG) host. This strategy allows for spontaneous loading of hydrophilic charged and non-charged functional modules onto the PEG surface without the need for catalysts or binding groups. The reversible insertion of the hydrophobic anchor enables programmable surface functionalization, challenging the current understanding of PEG in hydrophilicity and potentially advancing nanomedicine, advanced materials, and nanotechnology.
Article
Physics, Multidisciplinary
Antonio Suma, Vincenzo Carnevale, Cristian Micheletti
Summary: Using theory and simulations, the authors studied DNA unzipping via nanopore translocation and found three dynamical regimes depending on the applied force. They showed that the normal regime can be modeled as a one-dimensional stochastic process and used the theory of stochastic processes to recover the free-energy landscape. This approach can be applied to other single-molecule systems with periodic potentials to obtain detailed free-energy landscapes from out-of-equilibrium trajectories.
PHYSICAL REVIEW LETTERS
(2023)
Article
Chemistry, Medicinal
Phu K. Tang, Prabir Khatua, Vincenzo Carnevale, Sharon M. Loverde
Summary: In this study, the initial stages of self-assembly of a model drug amphiphile in an aqueous solution were characterized through atomistic molecular dynamics simulations. It was found that aromatic stacking of the drug molecules drove the formation of a higher-density liquid droplet, which elongated and formed a higher-ordered supramolecular assembly through reorganization and additional aromatic stacking. The development of novel reaction coordinates tailored to this class of molecules was shown to be essential in capturing the degree of molecular order during assembly. This approach can be extended to study the supramolecular assembly pathway of other molecules containing aromatic compounds.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2023)
Article
Chemistry, Physical
Mohsen Farshad, Mark J. DelloStritto, Antonio Sum, Vincenzo Carneval
Summary: In this study, we analyzed a methanol/hexane mixture to investigate the phase diagram and structural changes associated with demixing. We found that the topological properties of the H-bond network abruptly change as the system crosses the demixing line, which can be detected using spectral clustering. We further validated the effectiveness of spectral clustering analysis in detecting demixing transitions in a Lennard-Jones system without H-bonds.
JOURNAL OF PHYSICAL CHEMISTRY B
(2023)
Review
Biochemistry & Molecular Biology
Matthew Gabrielle, Tibor Rohacs
Summary: TMEM120A is a mysterious protein with multiple seemingly unrelated functions. It was initially proposed to be an ion channel involved in mechanical sensing and pain sensation, but its ion channel function has been challenged. However, it still impacts mechanosensation by inhibiting PIEZO2 channels and modifying tactile pain responses. TMEM120A also interacts with polycystin-2 (PKD2) channels and is involved in adipocyte regulation and innate immune response against Zika virus.
Article
Chemistry, Medicinal
Phu K. Tang, Prabir Khatua, Vincenzo Carnevale, Sharon M. Loverde
Summary: The initial stages of self-assembly of a model drug amphiphile in an aqueous solution were characterized using atomistic molecular dynamics simulations. Two-dimensional metadynamics calculations were performed to understand the assembly space of the model drug amphiphile Tubustecan, TT1. Aromatic stacking of the hydrophobic anticancer drug, Camptothecin (CPT), was found to drive the formation of a higher-density liquid droplet, which elongates and forms a higher-ordered supramolecular assembly through reorganization and additional aromatic stacking of the drugs. Novel reaction coordinates tailored to this class of molecules were shown to be essential in capturing the underlying degree of molecular order during assembly. This approach can be further refined and extended to study the supramolecular assembly pathway of other molecules containing aromatic compounds.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2023)
Article
Chemistry, Multidisciplinary
Shaohua Zhang, Abhinav Srivastava, Wei Li, Sjoerd J. Rijpkema, Vincenzo Carnevale, Michael L. Klein, Daniela A. Wilson
Summary: An adaptive surface that can detect and respond to environmental changes is crucial for smart functional materials. This study presents a pH-responsive anchoring system on the poly(ethylene glycol) (PEG) corona of polymer vesicles. By reversibly protonating the covalently linked pH-sensing group, the hydrophobic anchor pyrene can be inserted into the PEG corona. The pH-responsive region can be engineered from acidic to neutral and basic conditions depending on the sensor's pKa. The switchable electrostatic repulsion between the sensors contributes to the responsive anchoring behavior. These findings offer a new responsive binding chemistry for the development of smart nanomedicine and nanoreactors.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)