The Experts below are selected from a list of 294 Experts worldwide ranked by ideXlab platform
Ming-chang Lin - One of the best experts on this subject based on the ideXlab platform.
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a model study of co co adsorbate interaction on si 100 2 1
Journal of Physical Chemistry B, 1999Co-Authors: F Bacalzogladden, Ming-chang LinAbstract:The CO−CO adsorbate interaction on Si(100)-2×1 has been investigated with ab initio molecular orbital and hybrid density functional theory calculations using cluster models of the surface. Different adsorption combinations for one and two CO molecules on single- and double-dimer cluster models, Si9H12 and Si15H16, respectively, are described. Our calculations indicate that the second CO molecule is physisorbed on the same surface Si dimer where the first CO molecule is chemisorbed. The chemisorption of the first CO molecule induces a change in the charge of the surface Si dimer atoms which inhibits further adsorbate−surface interaction. The dissociation energy of the physisorbed second CO molecule is less than 1 kcal/mol. Adsorption of the second CO molecule on the second Si dimer is energetically preferred over coadsorption of CO on the same Si dimer. The 2OC-normal.d14 structure is the most stable configuration, with the two CO molecules adsorbed diagonally across the two Si dimers. The dissociation ene...
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A model study of CO-CO adsorbate interaction on Si(100)-2×1
The Journal of Physical Chemistry B, 1999Co-Authors: F. Bacalzo-gladden, Ming-chang LinAbstract:The CO−CO adsorbate interaction on Si(100)-2×1 has been investigated with ab initio molecular orbital and hybrid density functional theory calculations using cluster models of the surface. Different adsorption combinations for one and two CO molecules on single- and double-dimer cluster models, Si9H12 and Si15H16, respectively, are described. Our calculations indicate that the second CO molecule is physisorbed on the same surface Si dimer where the first CO molecule is chemisorbed. The chemisorption of the first CO molecule induces a change in the charge of the surface Si dimer atoms which inhibits further adsorbate−surface interaction. The dissociation energy of the physisorbed second CO molecule is less than 1 kcal/mol. Adsorption of the second CO molecule on the second Si dimer is energetically preferred over coadsorption of CO on the same Si dimer. The 2OC-normal.d14 structure is the most stable configuration, with the two CO molecules adsorbed diagonally across the two Si dimers. The dissociation ene...
Akihiro Kusumi - One of the best experts on this subject based on the ideXlab platform.
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Single-molecule imaging revealed dynamic GPCR dimerization
Current opinion in cell biology, 2013Co-Authors: Rinshi S Kasai, Akihiro KusumiAbstract:Single fluorescent-molecule video imaging and tracking in living cells are revolutionizing our understanding of molecular interactions in the plasma membrane and intracellular membrane systems. They have revealed that molecular interactions occur surprisingly dynamically on much shorter time scales (≪1s) than those expected from the results by conventional techniques, such as pull-down assays (minutes to hours). Single-molecule imaging has unequivocally showed that G-protein-coupled receptors (GPCRs) undergo dynamic equilibrium between monomers and dimers, by enabling the determination of the 2D monomer-dimer equilibrium constant, the dimer dissociation rate constant (typically ∼10s(-1)), and the formation rate constant. Within one second, GPCRs typically undergo several cycles of monomer and homo-dimer formation with different partners.
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full characterization of gpcr monomer dimer dynamic equilibrium by single molecule imaging
Journal of Cell Biology, 2011Co-Authors: Rinshi S Kasai, Kenichi G N Suzuki, Eric R Prossnitz, Ikuko Koyamahonda, Chieko Nakada, Takahiro K Fujiwara, Akihiro KusumiAbstract:Receptor dimerization is important for many signaling pathways. However, the monomer–dimer equilibrium has never been fully characterized for any receptor with a 2D equilibrium constant as well as association/dissociation rate constants (termed super-quantification). Here, we determined the dynamic equilibrium for the N-formyl peptide receptor (FPR), a chemoattractant G protein–coupled receptor (GPCR), in live cells at 37°C by developing a single fluorescent-molecule imaging method. Both before and after liganding, the dimer–monomer 2D equilibrium is unchanged, giving an equilibrium constant of 3.6 copies/µm2, with a dissociation and 2D association rate constant of 11.0 s−1 and 3.1 copies/µm2s−1, respectively. At physiological expression levels of ∼2.1 receptor copies/µm2 (∼6,000 copies/cell), monomers continually convert into dimers every 150 ms, dimers dissociate into monomers in 91 ms, and at any moment, 2,500 and 3,500 receptor molecules participate in transient dimers and monomers, respectively. Not only do FPR dimers fall apart rapidly, but FPR monomers also convert into dimers very quickly.
Krishna Rajarathnam - One of the best experts on this subject based on the ideXlab platform.
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chemokine cxcl1 mediated neutrophil trafficking in the lung role of cxcr2 activation
Journal of Innate Immunity, 2015Co-Authors: Kirti V Sawant, Renling Xu, Hal K Hawkins, Elena Sbrana, Deepthi Kolli, Roberto P Garofalo, Krishna RajarathnamAbstract:The chemokine CXCL1 and its receptor CXCR2 play a crucial role in host immune response by recruiting and activating neutrophils for microbial killing at the tissue site. Dysregulation in this process has been implicated in collateral tissue damage causing disease. CXCL1 reversibly exists as monomers and dimers, and it has been proposed that distinct monomer and dimer activities and the monomer-dimer equilibrium regulate the neutrophil function. However, the molecular mechanisms linking the CXCL1/CXCR2 axis and the neutrophil ‘beneficial' and ‘destructive' phenotypes are not known. In this study, we characterized neutrophil trafficking and its consequence in the mouse lung by the CXCL1 wild type (WT), which exists as monomers and dimers, and by a nondissociating dimer. Whereas the WT, compared to the dimer, was more active at low doses, both the WT and the dimer elicited a large neutrophil efflux at high doses. Importantly, robust neutrophil recruitment elicited by the WT or dimer was not detrimental to lung tissue integrity and, further, could not be correlated to surface CXCR2 levels. We conclude that the CXCL1 monomer-dimer distribution and receptor interactions are highly coupled and regulate neutrophil trafficking and that injury in the context of disease is a consequence of inappropriate CXCR2 activation at the target tissue and not due to mechanical forces exerted by neutrophils during recruitment.
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Solution NMR characterization of chemokine CXCL8/IL-8 monomer and dimer binding to glycosaminoglycans: structural plasticity mediates differential binding interactions
The Biochemical journal, 2015Co-Authors: Prem Raj B. Joseph, Philip D. Mosier, Umesh R. Desai, Krishna RajarathnamAbstract:Chemokine CXCL8/interleukin-8 (IL-8) plays a crucial role in directing neutrophils and oligodendrocytes to combat infection/injury and tumour cells in metastasis development. CXCL8 exists as monomers and dimers and interaction of both forms with glycosaminoglycans (GAGs) mediate these diverse cellular processes. However, very little is known regarding the structural basis underlying CXCL8-GAG interactions. There are conflicting reports on the affinities, geometry and whether the monomer or dimer is the high-affinity GAG ligand. To resolve these issues, we characterized the binding of a series of heparin-derived oligosaccharides [heparin disaccharide (dp2), heparin tetrasaccharide (dp4), heparin octasaccharide (dp8) and heparin 14-mer (dp14)] to the wild-type (WT) dimer and a designed monomer using solution NMR spectroscopy. The pattern and extent of binding-induced chemical shift perturbation (CSP) varied between dimer and monomer and between longer and shorter oligosaccharides. NMR-based structural models show that different interaction modes coexist and that the nature of interactions varied between monomer and dimer and oligosaccharide length. MD simulations indicate that the binding interface is structurally plastic and provided residue-specific details of the dynamic nature of the binding interface. Binding studies carried out under conditions at which WT CXCL8 exists as monomers and dimers provide unambiguous evidence that the dimer is the high-affinity GAG ligand. Together, our data indicate that a set of core residues function as the major recognition/binding site, a set of peripheral residues define the various binding geometries and that the structural plasticity of the binding interface allows multiplicity of binding interactions. We conclude that structural plasticity most probably regulates in vivo CXCL8 monomer/dimer-GAG interactions and function.
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chemokine cxcl1 dimer is a potent agonist for the cxcr2 receptor
Journal of Biological Chemistry, 2013Co-Authors: Aishwarya Ravindran, Jose Sarmiento, Javier Navarro, Kirti V Sawant, Krishna RajarathnamAbstract:Abstract The CXCL1/CXCR2 axis plays a crucial role in recruiting neutrophils in response to microbial infection and tissue injury, and dysfunction in this process has been implicated in various inflammatory diseases. Chemokines exist as monomers and dimers, and compelling evidence now exists that both forms regulate in vivo function. Therefore, knowledge of the receptor activities of both CXCL1 monomer and dimer is essential to describe the molecular mechanisms by which they orchestrate neutrophil function. The monomer-dimer equilibrium constant (∼20 μm) and the CXCR2 binding constant (1 nm) indicate that WT CXCL1 is active as a monomer. To characterize dimer activity, we generated a trapped dimer by introducing a disulfide across the dimer interface. This disulfide-linked CXCL1 dimer binds CXCR2 with nanomolar affinity and shows potent agonist activity in various cellular assays. We also compared the receptor binding mechanism of this dimer with that of a CXCL1 monomer, generated by deleting the C-terminal residues that stabilize the dimer interface. We observe that the binding interactions of the dimer and monomer to the CXCR2 N-terminal domain, which plays an important role in determining affinity and activity, are essentially conserved. The potent activity of the CXCL1 dimer is novel: dimers of the CC chemokines CCL2 and CCL4 are inactive, and the dimer of the CXC chemokine CXCL8 (which is closely related to CXCL1) is marginally active for CXCR1 but shows variable activity for CXCR2. We conclude that large differences in dimer activity among different chemokine-receptor pairs have evolved for fine-tuned leukocyte function.
Rinshi S Kasai - One of the best experts on this subject based on the ideXlab platform.
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Single-molecule imaging revealed dynamic GPCR dimerization
Current opinion in cell biology, 2013Co-Authors: Rinshi S Kasai, Akihiro KusumiAbstract:Single fluorescent-molecule video imaging and tracking in living cells are revolutionizing our understanding of molecular interactions in the plasma membrane and intracellular membrane systems. They have revealed that molecular interactions occur surprisingly dynamically on much shorter time scales (≪1s) than those expected from the results by conventional techniques, such as pull-down assays (minutes to hours). Single-molecule imaging has unequivocally showed that G-protein-coupled receptors (GPCRs) undergo dynamic equilibrium between monomers and dimers, by enabling the determination of the 2D monomer-dimer equilibrium constant, the dimer dissociation rate constant (typically ∼10s(-1)), and the formation rate constant. Within one second, GPCRs typically undergo several cycles of monomer and homo-dimer formation with different partners.
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full characterization of gpcr monomer dimer dynamic equilibrium by single molecule imaging
Journal of Cell Biology, 2011Co-Authors: Rinshi S Kasai, Kenichi G N Suzuki, Eric R Prossnitz, Ikuko Koyamahonda, Chieko Nakada, Takahiro K Fujiwara, Akihiro KusumiAbstract:Receptor dimerization is important for many signaling pathways. However, the monomer–dimer equilibrium has never been fully characterized for any receptor with a 2D equilibrium constant as well as association/dissociation rate constants (termed super-quantification). Here, we determined the dynamic equilibrium for the N-formyl peptide receptor (FPR), a chemoattractant G protein–coupled receptor (GPCR), in live cells at 37°C by developing a single fluorescent-molecule imaging method. Both before and after liganding, the dimer–monomer 2D equilibrium is unchanged, giving an equilibrium constant of 3.6 copies/µm2, with a dissociation and 2D association rate constant of 11.0 s−1 and 3.1 copies/µm2s−1, respectively. At physiological expression levels of ∼2.1 receptor copies/µm2 (∼6,000 copies/cell), monomers continually convert into dimers every 150 ms, dimers dissociate into monomers in 91 ms, and at any moment, 2,500 and 3,500 receptor molecules participate in transient dimers and monomers, respectively. Not only do FPR dimers fall apart rapidly, but FPR monomers also convert into dimers very quickly.
F Bacalzogladden - One of the best experts on this subject based on the ideXlab platform.
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a model study of co co adsorbate interaction on si 100 2 1
Journal of Physical Chemistry B, 1999Co-Authors: F Bacalzogladden, Ming-chang LinAbstract:The CO−CO adsorbate interaction on Si(100)-2×1 has been investigated with ab initio molecular orbital and hybrid density functional theory calculations using cluster models of the surface. Different adsorption combinations for one and two CO molecules on single- and double-dimer cluster models, Si9H12 and Si15H16, respectively, are described. Our calculations indicate that the second CO molecule is physisorbed on the same surface Si dimer where the first CO molecule is chemisorbed. The chemisorption of the first CO molecule induces a change in the charge of the surface Si dimer atoms which inhibits further adsorbate−surface interaction. The dissociation energy of the physisorbed second CO molecule is less than 1 kcal/mol. Adsorption of the second CO molecule on the second Si dimer is energetically preferred over coadsorption of CO on the same Si dimer. The 2OC-normal.d14 structure is the most stable configuration, with the two CO molecules adsorbed diagonally across the two Si dimers. The dissociation ene...
