@article {48207, title = {Copper(II) import and reduction are dependent on His-Met clusters in the extracellular amino terminus of human copper transporter-1}, journal = {Journal of Biological Chemistry}, volume = {298}, year = {2022}, month = {MAR}, pages = {101631}, type = {Article}, abstract = {

Copper(I) is an essential metal for all life forms. Though Cu(II) is the most abundant and stable state, its reduction to Cu(I) via an unclear mechanism is prerequisite for its bioutilization. In eukaryotes, the copper transporter-1(CTR1) is the primary high-affinity copper importer, although its mechanism and role in Cu(II) reduction remain uncharacterized. Here we show that extracellular amino-terminus of human CTR1 contains two methionine-histidine clusters and neighboring aspartates that distinctly bind Cu(I) and Cu(II) preceding its import. We determined that hCTR1 localizes at the basolateral membrane of polarized MDCK-II cells and that its endocytosis to Common-Recycling-Endosomes is regulated by reduction of Cu(II) to Cu(I) and subsequent Cu(I) coordination by the methionine cluster. We demonstrate the transient binding of both Cu(II) and Cu(I) during the reduction process is facilitated by aspartates that also act as another crucial determinant of hCTR1 endocytosis. Mutating the first Methionine cluster ((7)Met-Gly-Met(9)) and Asp(13)( )abrogated copper uptake and endocytosis upon copper treatment. This phenotype could be reverted by treating the cells with reduced and nonreoxidizable Cu(I). We show that histidine clusters, on other hand, bind Cu(II) and are crucial for hCTR1 functioning at limiting copper. Finally, we show that two N-terminal His-Met-Asp clusters exhibit functional complementarity, as the second cluster is sufficient to preserve copper-induced CTR1 endocytosis upon complete deletion of the first cluster. We propose a novel and detailed mechanism by which the two His-Met-Asp residues of hCTR1 amino-terminus not only bind copper, but also maintain its reduced state, crucial for intracellular uptake.

}, doi = {10.1016/j.jbc.2022.101631}, author = {Kar, Sumanta and Sen, Samarpita and Maji, Saptarshi and Saraf, Deepashri and Ruturaj and Paul, Rupam and Dutt, Sohini and Mondal, Basudeb and Rodriguez-Boulan, Enrique and Schreiner, Ryan and Sengupta, Durba and Gupta, Arnab} } @article {48719, title = {Molecular mechanisms underlying nanowire formation in pristine phthalocyanine}, journal = {Physical Chemistry Chemical Physics}, volume = {25}, year = {2023}, month = {NOV}, pages = {30259-30268}, type = {Article}, abstract = {

Understanding the molecular processes of nanowire self-assembly is crucial for designing and controlling nanoscale structures that could lead to breakthroughs in functional materials. In this work, we focus on pristine phthalocyanines as a representative example of mesogenic supramolecular assemblies and have analyzed the formation of nanowires using classical molecular dynamics simulations. In the simulations, the molecules spontaneously form multi-columnar structures resembling supramolecular polymers that subsequently grow into more ordered aggregates. These self-assemblies are concentration dependent, leading to the formation of multi-columnar, dynamic aggregates at higher concentrations and nanowires at lower concentrations. The multi-columnar assemblies on a whole are more disordered than the nanowires, but have locally ordered domains of parallel facing molecules that can fluctuate while maintaining their overall shape. The nanowire formation at lower concentrations involves the initial interaction and clustering of randomly oriented phthalocyanine molecules, followed by the merging of small clusters into elongated segments and the eventual formation of a stable nanowire. We observe three main conformers in these self-assemblies, the parallel, T-shaped and edge-to-edge stacking of the phthalocyanine dimers. We calculate the underlying free energy landscape and show that the parallel conformers form the most stable configuration which is followed by the T-shaped and edge-to-edge dimer configurations. The findings provide insights into the mechanisms and pathways of nanowire formation and a step towards the understanding of self-assembly processes in supramolecular mesogens. Understanding the molecular processes of nanowire self-assembly of phthalocyanine molecules.

}, issn = {1463-9076}, doi = {10.1039/d3cp03512c}, author = {Pinjari, Aadil and Saraf, Deepashri and Sengupta, Durba} } @article {48463, title = {Surface-induced demixing of self-assembled isomeric mixtures of citral}, journal = {Journal of Molecular Liquids}, volume = {381}, year = {2023}, month = {JUL }, pages = {121803}, type = {Article}, abstract = {

The self-assembly of organic molecules and their interactions with metal surfaces have been of considerable interest, both for developing novel functional materials and for understanding fundamental design principles of nanostructures. In this study, we investigate the solution and surface-induced self-assembly of two stereoisomers of citral molecules (geranial and neral) using atomistic molecular dynamics simulations. We demonstrate that the morphology of the aggregates in water is concentration dependent (ranging from distorted spherical to slab-like aggregates) but independent of isomer effects. The isomeric mixtures of citral indicate homogeneous mixing based on differential density maps and high values of Shannon entropy. Interestingly, surface-confinement of citral aggregates on a Cu(111) surface leads to phase segregation and demixing of the two isomers that is more apparent in the surface-bound monolayer in comparison to the adjacent layers. Positional ordering and formation of domains are observed over a series of isomeric citral mixtures with varying compositions, as indicated by high differential density and low values of Shannon entropy. Our work provides new insights into molecular self-assembly of organic molecules in nanostructures and metal-organic overlayers.(c) 2023 Elsevier B.V. All rights reserved.

}, keywords = {Citral, Isomers, Metal-organic interactions, molecular dynamics, Self-assembly, Shannon entropy}, issn = {0167-7322}, doi = {10.1016/j.molliq.2023.121803}, author = {Saraf, Deepashri and Prakash, Shikha and Pinjari, Aadil and Pujari, Bhalchandra and Sengupta, Durba} } @article {49408, title = {Effect of citral partitioning on structural and mechanical properties of lipid membranes}, journal = {European Physical Journal-Special Topics}, volume = {233}, year = {2024}, month = {DEC}, pages = {3009-3021}, type = {Article}, abstract = {

Delineating the interactions of cellular metabolites with lipid membranes and their effects on membrane physical and mechanical properties constitutes a key step for comprehensively understanding their biological function. The plant metabolite-citral is widely used in biotechnological and cosmeceutical processes, but significant gaps remain in our understanding of how it affects cellular membranes that it interacts with. In this study, we unravel the molecular mechanisms underlying the interactions of citral with compositionally distinct model membranes using atomistic molecular dynamics simulations. Specifically, we investigate two distinct membrane compositions: the neutral phosphatidylcholine-phosphatidylethanolamine (DOPC:DOPE) bilayer, representing mammalian cell membranes and the anionic phosphatidylcholine-phosphatidylglycerol (DOPC:DOPG) bilayer, mimicking bacterial cell membranes. Our simulations reveal that citral molecules readily partition into both membranes without distinct composition-dependent effects. Monomeric citral molecules localize mainly at the interface of the acyl chain region of the lipids, and a few translocation events are sampled in the simulations. Interestingly, we observe small differences in lipid fluidity although the citral molecules significantly influence the rigidity of lipid bilayers, and a higher bending modulus was observed in DOPC:DOPE lipid bilayers compared to DOPC:DOPG bilayers. Further, citral partitioning induces an increased tendency for lipid demixing in DOPC:DOPE membranes, as evidenced by the decreased values of the Shannon entropy. Our work is an important step to elucidate the molecular processes that underlie the differential impact of cell metabolites on compositionally distinct lipid membranes.

}, issn = {1951-6355}, doi = {10.1140/epjs/s11734-024-01147-w}, author = {Saraf, Deepashri and Porte, Sudha and Sengupta, Durba} }