Biology subjects

Schmid, E. M.

Publications and source records attributed to Schmid, E. M..

3 recordsLinked to original sources

bioRxiv2020

Variable optical properties of light-harvesting complex II revisited

Understanding photosynthetic light harvesting requires knowledge of the molecular mechanisms that dissipate excess energy in thylakoids. However, it remains unclear how the physical environment of light-harvesting complex II (LHCII) influences the process of chlorophyll de-excitation. Here, we demonstrate that protein-protein interactions between LHCIIs affect the optical properties of LHCII and thus influence the total energy budget. Aggregation of LHCII in the dark altered its absorption properties, independent of the amount of prior light exposure. We also revisited the triplet excited state involved in light-induced fluorescence quenching and found another relaxation pathway involving emission in the green region, which might be related to triplet excited energy transfer to neighboring carotenoids and annihilation processes that result in photoluminescence. LHCII- containing liposomes with different protein densities exhibited altered fluorescence and scattering properties. Our results suggest that macromolecular reorganization affects overall optical properties, which need to be addressed to compare the level of energy dissipation.

plant biology↗

bioRxiv2020

Antibody:CD47 ratio regulates macrophage phagocytosis through competitive receptor phosphorylation

Cancer immunotherapies often modulate macrophage effector function by introducing either targeting antibodies that activate Fc gamma receptors or blocking antibodies that disrupt inhibitory SIRP-CD47 engagement. Yet how these competing signals are integrated is poorly understood mechanistically, raising questions about how to effectively titrate immune responses. Here we find that macrophage phagocytic decisions are regulated by the ratio of activating ligand to inhibitory ligand on targets over a broad range of absolute molecular densities. Using endogenous as well as chimeric receptors, we show that activating:inhibitory ligand ratios of at least 10:1 are required to promote phagocytosis of model antibody-opsonized CD47-inhibited targets and that lowering this ratio reduces Fc{gamma}R phosphorylation due to inhibitory phosphatases recruited to CD47-bound SIRP. We demonstrate that ratiometric signaling is critical for phagocytosis of tumor cells and can be modified by blocking SIRP in vitro, indicating that balancing targeting and blocking antibodies may be important for controlling macrophage phagocytosis in cancer immunotherapy.

immunology↗

bioRxiv2019

A viral fusogen hijacks the actin cytoskeleton to drive cell-cell fusion

Cell-cell fusion, which is essential for tissue development and used by some viruses to form pathological syncytia, is typically driven by fusogenic membrane proteins with tall (>10 nm) ectodomains that undergo conformational changes to bring apposing membranes in close contact prior to fusion. Here we report that a viral fusogen with a short (<2 nm) ectodomain, the reptilian orthoreovirus p14, accomplishes the same task by hijacking the actin cytoskeleton. We show that the cytoplasmic domain of p14 triggers N-WASP-mediated assembly of a branched actin network, directly coupling local force generation with a short membrane-disruptive ectodomain. This work reveals that overcoming energetic barriers to cell-cell fusion does not require conformational changes of tall fusogens but can instead be driven by harnessing the host cytoskeleton.\n\nImpact StatementA viral fusogen drives cell-cell fusion by hijacking the actin machinery to directly couple actin assembly with a short fusogenic ectodomain.

cell biology↗