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Chloroplasts rely on the translocon complexes in the outer and inner envelope membranes (the TOC and TIC complexes, respectively) to import thousands of different nuclear-encoded proteins from the cytosol 1 – 4 . Although previous studies indicated that the TOC and TIC complexes may assemble into larger supercomplexes 5 – 7 , the overall architectures of the TOC–TIC supercomplexes and the mechanism of preprotein translocation are unclear. Here we report the cryo-electron microscopy structure of the TOC–TIC supercomplex from Chlamydomonas reinhardtii . The major subunits of the TOC complex (Toc75, Toc90 and Toc34) and TIC complex (Tic214, Tic20, Tic100 and Tic56), three chloroplast translocon-associated proteins (Ctap3, Ctap4 and Ctap5) and three newly identified small inner-membrane proteins (Simp1–3) have been located in the supercomplex. As the largest protein, Tic214 traverses the inner membrane, the intermembrane space and the outer membrane, connecting the TOC complex with the TIC proteins. An inositol hexaphosphate molecule is located at the Tic214–Toc90 interface and stabilizes their assembly. Four lipid molecules are located within or above an inner-membrane funnel formed by Tic214, Tic20, Simp1 and Ctap5. Multiple potential pathways found in the TOC–TIC supercomplex may support translocation of different substrate preproteins into chloroplasts. A cryo-electron microscopy analysis of the Chlamydomonas reinhardtii TOC–TIC supercomplex reveals that Tic214 traverses the chloroplast inner membrane, the intermembrane space and the outer membrane, connecting the TOC complex with the TIC proteins.

As a large family of membrane proteins crucial for bacterial physiology and virulence, the Multiple Peptide Resistance Factors (MprFs) utilize two separate domains to synthesize and translocate aminoacyl phospholipids to the outer leaflets of bacterial membranes. The function of MprFs enables Staphylococcus aureus and other pathogenic bacteria to acquire resistance to daptomycin and cationic antimicrobial peptides. Here we present cryo-electron microscopy structures of MprF homodimer from Rhizobium tropici ( Rt MprF) at two different states in complex with lysyl-phosphatidylglycerol (LysPG). Rt MprF contains a membrane-embedded lipid-flippase domain with two deep cavities opening toward the inner and outer leaflets of the membrane respectively. Intriguingly, a hook-shaped LysPG molecule is trapped inside the inner cavity with its head group bent toward the outer cavity which hosts a second phospholipid-binding site. Moreover, Rt MprF exhibits multiple conformational states with the synthase domain adopting distinct positions relative to the flippase domain. Our results provide a detailed framework for understanding the mechanisms of MprF-mediated modification and translocation of phospholipids. The Multiple Peptide Resistance Factors (MprFs) utilize two separate domains to synthesize and translocate aminoacyl phospholipids to the outer leaflets of bacterial membranes. Here authors present cryo-electron microscopy structures of MprF homodimer from Rhizobium tropici ( Rt MprF) at two different states in complex with lysyl-phosphatidylglycerol (LysPG).

In plants, the photosynthetic machinery photosystem II (PSII) consists of a core complex associated with variable numbers of light-harvesting complexes II (LHCIIs). The supercomplex, comprising a dimeric core and two strongly bound and two moderately bound LHCIIs (C₂S₂M₂), is the dominant form in plants acclimated to limited light. Here we report cryo–electron microscopy structures of two forms of C₂S₂M₂ (termed stacked and unstacked) from Pisum sativum at 2.7- and 3.2-angstrom resolution, respectively. In each C₂S₂M₂, the moderately bound LHCII assembles specifically with a peripheral antenna complex CP24-CP29 heterodimer and the strongly bound LHCII, to establish a pigment network that facilitates light harvesting at the periphery and energy transfer into the core. The high mobility of peripheral antennae, including the moderately bound LHCII and CP24, provides insights into functional regulation of plant PSII.

During photosynthesis, the plant photosystem II core complex receives excitation energy from the peripheral light-harvesting complex II (LHCII). The pathways along which excitation energy is transferred between them, and their assembly mechanisms, remain to be deciphered through high-resolution structural studies. Here we report the structure of a 1.1-megadalton spinach photosystem II–LHCII supercomplex solved at 3.2 Å resolution through single-particle cryo-electron microscopy. The structure reveals a homodimeric supramolecular system in which each monomer contains 25 protein subunits, 105 chlorophylls, 28 carotenoids and other cofactors. Three extrinsic subunits (PsbO, PsbP and PsbQ), which are essential for optimal oxygen-evolving activity of photosystem II, form a triangular crown that shields the Mn 4 CaO 5 -binding domains of CP43 and D1. One major trimeric and two minor monomeric LHCIIs associate with each core-complex monomer, and the antenna–core interactions are reinforced by three small intrinsic subunits (PsbW, PsbH and PsbZ). By analysing the closely connected interfacial chlorophylls, we have obtained detailed insights into the energy-transfer pathways between the antenna and core complexes. A high-resolution structural study sheds light on processes of energy transfer within the photosynthetic water-splitting machinery of plants. Energy transfer in the photosynthetic complex The conversion of light into usable energy within a photosynthesizing cell occurs within the light-harvesting complex (LHC) and photosystem (PS) complex. To understand this process, it is critical to know how excitation energy is transferred from the peripheral LHC antenna to the core PS structure. Zhenfeng Liu and colleagues have determined a high-resolution structure of a 1.1-MDa plant PSII–LHCII supercomplex by single-particle cryo-electron microscopy. They find that each monomer of the homodimeric supercomplex contains 25 proteins and 133 pigment cofactors. Some differences are seen compared to cyanobacterial PSII structures, but, most importantly, the ability to examine the PSII–LHCII interface permits solid predictions regarding the excitation-energy-transfer pathway.

Photosystem II (PSII) catalyzes water oxidation and plastoquinone reduction by utilizing light energy. It is highly susceptible to photodamage under high-light conditions and the damaged PSII needs to be restored through a process known as the PSII repair cycle. The detailed molecular mechanism underlying the PSII repair process remains mostly elusive. Here, we report biochemical and structural features of a PSII-repair intermediate complex, likely arrested at an early stage of the PSII repair process in the green alga Chlamydomonas reinhardtii . The complex contains three protein factors associated with a damaged PSII core, namely Thylakoid Enriched Factor 14 (TEF14), Photosystem II Repair Factor 1 (PRF1), and Photosystem II Repair Factor 2 (PRF2). TEF14, PRF1 and PRF2 may facilitate the release of the manganese-stabilizing protein PsbO, disassembly of peripheral light-harvesting complexes from PSII and blockage of the Q B site, respectively. Moreover, an α-tocopherol quinone molecule is located adjacent to the heme group of cytochrome b 559 , potentially fulfilling a photoprotective role by preventing the generation of reactive oxygen species. Here the authors show an intermediate state of the photosystem II (PSII) repair cycle, where three protein factors and an α-tocopherol quinone molecule are associated with a damaged PSII at distinct sites, fulfilling their specific functions in the repair process.

Ovarian cancer (OC) stands as a formidable adversary among women, remaining a leading cause of cancer-related mortality owing to its aggressive and invasive nature. Investigating prognostic markers intricately linked to OC's molecular pathogenesis represents a critical avenue for enhancing patient outcomes and survival prospects. In this comprehensive study, we embarked on a bioinformatics journey, leveraging the vast repository of single nucleotide polymorphism (SNP) data from OC patients available within the TCGA database. Our overarching goal was to unearth the genetic underpinnings of OC, shedding light on potential prognostic markers that could significantly impact clinical decision-making and patient care. Our meticulous analysis led to the discovery of five mutated genes—APOB, BRCA1, COL6A3, LRP1, and LRP1B—engaged in the intricate world of lipid metabolism. These genes, previously unexplored in the context of OC, emerged as prominent figures in our investigation, showcasing their potential roles in OC progression. The intricate interplay between lipid metabolism and cancer development has garnered considerable attention in recent years, and our findings underscore the relevance of these genes in the context of OC. To fortify our discoveries, we delved into the realm of survival analysis, a pivotal component of our investigation. The results yielded compelling evidence of significant correlations between patient survival and the expression levels of the aforementioned genes. This critical insight underscores the potential utility of these genes as prognostic markers, illuminating a path toward more personalized and effective approaches to patient care. Our study represents a multifaceted approach to unraveling the complex molecular pathogenesis of OC. By harnessing the power of high-throughput data mining, we uncovered genetic insights that may reshape our understanding of this formidable disease. We complemented these findings with advanced techniques such as RT-qPCR and Western blot, further dissecting the intricacies of OC's molecular landscape. This holistic approach not only deepens our understanding but also provides essential bioinformatics information that holds promise in assessing patient prognosis. In summary, our study represents a significant stride in the quest to decode the molecular intricacies of ovarian cancer. Our findings spotlight the potential prognostic significance of APOB, BRCA1, COL6A3, LRP1, and LRP1B, inviting further exploration into their roles in OC progression. Ultimately, our research carries the potential to shape the future of OC management, offering a glimpse into a more personalized and effective approach to patient care.

Phospholipids are elemental building-block molecules for biological membranes. Biosynthesis of phosphatidylinositol, phosphatidylglycerol and phosphatidylserine requires a central liponucleotide intermediate named cytidine-diphosphate diacylglycerol (CDP-DAG). The CDP-DAG synthetase (Cds) is an integral membrane enzyme catalysing the formation of CDP-DAG, an essential step for phosphoinositide recycling during signal transduction. Here we report the structure of the Cds from Thermotoga maritima (TmCdsA) at 3.4 Å resolution. TmCdsA forms a homodimer and each monomer contains nine transmembrane helices arranged into a novel fold with three domains. An unusual funnel-shaped cavity penetrates half way into the membrane, allowing the enzyme to simultaneously accept hydrophilic substrate (cytidine 5′-triphosphate (CTP)/deoxy-CTP) from cytoplasm and hydrophobic substrate (phosphatidic acid) from membrane. Located at the bottom of the cavity, a Mg 2+ -K + hetero-di-metal centre coordinated by an Asp-Asp dyad serves as the cofactor of TmCdsA. The results suggest a two-metal-ion catalytic mechanism for the Cds-mediated synthesis of CDP-DAG at the membrane–cytoplasm interface. Cytidine-diphosphate diacylglycerol (CDP-DAG) is a central liponucleotide intermediate required for the biosynthesis of some phospholipids and is synthesized by CDP-DAG synthetase (Cds). Here, Liu et al . report the structure of a Cds that shows how it can accept hydrophilic and hydrophobic substrates, and suggest a mechanism that requires two metal ions.

PsbS is a transmembrane photosystem II protein essential for photoprotection in plants. Crystal structures show that PsbS is not a canonical pigment-binding protein and provide insights into its pH-dependent activation mechanism. The photosystem II protein PsbS has an essential role in qE-type nonphotochemical quenching, which protects plants from photodamage under excess light conditions. qE is initiated by activation of PsbS by low pH, but the mechanism of PsbS action remains elusive. Here we report the low-pH crystal structures of PsbS from spinach in its free form and in complex with the qE inhibitor N , N′ -dicyclohexylcarbodiimide (DCCD), revealing that PsbS adopts a unique folding pattern, and, unlike other members of the light-harvesting-complex superfamily, it is a noncanonical pigment-binding protein. Structural and biochemical evidence shows that both active and inactive PsbS form homodimers in the thylakoid membranes, and DCCD binding disrupts the lumenal intermolecular hydrogen bonds of the active PsbS dimer. Activation of PsbS by low pH during qE may involve a conformational change associated with altered lumenal intermolecular interactions of the PsbS dimer.

The emergence of the sharing economy has affected consumers and traditional manufacturers. We focus on product sharing and analyze its impacts on the manufacturer that offers sequential innovation products. We develop a two-period model in which a monopoly manufacturer sells an old product and introduces a new product in each period; in the same period, an owner who bought a product for self-use from the manufacturer in the previous period may rent the product out because of the low self-use value in this period. Our analysis reveals that the sharing market increases or decreases the manufacturer’s profit, and this is mainly determined by the moral hazard cost and the salvage value of sharing products. Furthermore, the sharing market has an insignificant effect on the upgrading of products, but there is a bumping-down effect on old products’ sales. Finally, the effect of the sharing market on the revenue of the owner and the sharing platform mostly depends on the risk of moral hazard, and it also affects the manufacturer’s product rollover strategy.

Photosystem II (PSII) is the pigment-protein complex catalysing light-induced water oxidation. In Arabidopsis thaliana, it includes three Lhcb4–6 proteins linking the core complex to peripheral trimeric antennae. While Lhcb5 and Lhcb6 are encoded by single genes, Lhcb4 is encoded by three isoforms: Lhcb4.1 and Lhcb4.2 , constitutively expressed, and Lhcb4.3 ( Lhcb8 ), which accumulates under prolonged abiotic stress. Lhcb8 substitutes for Lhcb4, preventing Lhcb6 accumulation and resulting in a smaller PSII with high quantum yield. Cryo-electron microscopy reveals that Lhcb8 has a shorter carboxy-terminal domain, lacks two chlorophylls, and interacts more tightly with the PSII core, inducing structural changes in the PSII antenna system, ultimately inhibiting the formation of PSII arrays and favouring plastoquinone diffusion. We suggest that dynamic Lhcb4 vs Lhcb8 expression allows for PSII acclimation to contrasting light conditions, offering the potential for engineering crops with improved light use efficiency. Arabidopsis thaliana mutants expressing Lhcb8, a stress-induced paralog to Lhcb4 reveal its role in tuning the light-harvesting system of Photosystem II under excess light and maintaining high quantum efficiency.