13 research outputs found
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Structural analysis of a trimeric assembly of the mitochondrial dynamin-like GTPase Mgm1.
The fusion of inner mitochondrial membranes requires dynamin-like GTPases, Mgm1 in yeast and OPA1 in mammals, but how they mediate membrane fusion is poorly understood. Here, we determined the crystal structure of Saccharomyces cerevisiae short Mgm1 (s-Mgm1) in complex with GDP. It revealed an N-terminal GTPase (G) domain followed by two helix bundles (HB1 and HB2) and a unique C-terminal lipid-interacting stalk (LIS). Dimers can form through antiparallel HB interactions. Head-to-tail trimers are built by intermolecular interactions between the G domain and HB2-LIS. Biochemical and in vivo analyses support the idea that the assembly interfaces observed here are native and critical for Mgm1 function. We also found that s-Mgm1 interacts with negatively charged lipids via both the G domain and LIS. Based on these observations, we propose that membrane targeting via the G domain and LIS facilitates the in cis assembly of Mgm1, potentially generating a highly curved membrane tip to allow inner membrane fusion
Loss of Dip2b leads to abnormal neural differentiation from mESCs
Abstract Background Disco-interacting protein 2 homolog B is a member of the Dip2 family encoded by the Dip2b gene. Dip2b is widely expressed in neuro-related tissues and is essential in axonal outgrowth during embryogenesis. Methods Dip2b knockout mouse embryonic stem cell line was established by CRISPR/Cas9 gene-editing technology. The commercial kits were utilized to detect cell cycle and growth rate. Flow cytometry, qRT-PCR, immunofluorescence, and RNA-seq were employed for phenotype and molecular mechanism assessment. Results Our results suggested that Dip2b is dispensable for the pluripotency maintenance of mESCs. Dip2b knockout could not alter the cell cycle and proliferation of mECSs, or the ability to differentiate into three germ layers in vitro. Furthermore, genes associated with axon guidance, channel activity, and synaptic membrane were significantly downregulated during neural differentiation upon Dip2b knockout. Conclusions Our results suggest that Dip2b plays an important role in neural differentiation, which will provide a valuable model for studying the exact mechanisms of Dip2b during neural differentiation
Chromosome-Level Reference Genome and Population Genomic Analysis Provide Insights into the Evolution and Improvement of Domesticated Mulberry (Morus alba)
Mulberry (Morus spp.) is the sole plant consumed by the domesticated silkworm. However, the genome of domesticated mulberry has not yet been sequenced, and the ploidy level of this species remains unclear. Here, we report a high-quality, chromosome-level domesticated mulberry (Morus alba) genome. Analysis of genomic data and karyotype analyses confirmed that M. alba is a diploid with 28 chromosomes (2n = 2x = 28). Population genomic analysis based on resequencing of 134 mulberry accessions classified domesticated mulberry into three geographical groups, namely, Taihu Basin of southeastern China (Hu mulberry), northern and southwestern China, and Japan. Hu mulberry had the lowest nucleotide diversity among these accessions and demonstrated obvious signatures of selection associated with environmental adaptation. Further phylogenetic analysis supports a previous proposal that multiple domesticated mulberry accessions previously classified as different species actually belong to one species. This study expands our understanding of genome evolution of the genus Morus and population structure of domesticated mulberry, which would facilitate mulberry breeding and improvement
Bone analysis using an aggregationâinduced emissionâactive iridium complex
Abstract Fluorescent analysis of bone provides valuable insights into bone structures. However, conventional dyes suffer from low specificity on bone tissue, small stokes shift, short fluorescent lifetime, and aggregationâcaused quenching effect, which result in low efficacy and artifacts. In this work, we design an aggregationâinduced emission (AIE)âactive iridium(III) complex (IrâBP2) as a highly selective, convenient, nondestructiveness, and dualâmode staining agent for bone analysis. IrâBP2 containing phosphonate groups selectively binds to hydroxyapatites, the main component of bone matrix, and exhibits turnâon AIE phosphorescence with prolonged lifetime. IrâBP2 exhibits promising biosafety and offers higher accuracy in staining calcium deposits than conventional Alizarin Red S staining assay when it is employed in realâtime monitoring of osteogenesis differentiation process. A readyâtoâuse staining spray of IrâBP2 is fabricated. By using fluorescent imaging and lifetime imaging, IrâBP2 staining provides valuable insights into bone microstructure analysis, microdamage diagnosis, and bone growth state identification. Further, IrâBP2 is successfully applied on a human spine vertebra for diagnosing bone invasiveness of eosinophilic granuloma, validating its clinical practice. This work presents a powerful tool in bone analysis and will lead to new approaches for the diagnosis and treatment of boneârelated diseases