Biology subjects

Zhou, H.

Publications and source records attributed to Zhou, H..

At least 289 records · Page 16Linked to original sources

bioRxiv2022

Dectin-1 Stimulation Promotes a Distinct Inflammatory Signature in the Setting of HIV-infection and Aging

Dectin-1 is an innate immune receptor that recognizes and binds {beta}-1,3/1,6 glucans on fungi. We evaluated Dectin-1 function in myeloid cells in a cohort of HIV-positive and HIV-negative young and older adults. Stimulation of monocytes with {beta}-D-glucans induced a pro-inflammatory phenotype in monocytes of HIV-infected individuals that was characterized by increased levels of IL-12, TNF-, and IL-6, with some age-associated cytokine increases also noted. Dendritic cells showed a striking HIV-associated increase in IFN- production. These increases in cytokine production paralleled increases in Dectin-1 surface expression in both monocytes and dendritic cells that were noted with both HIV and aging. Differential gene expression analysis showed that HIV-positive older adults had a distinct gene signature compared to other cohorts characterized by a robust TNF- and coagulation response (increased at baseline), a persistent IFN- and IFN-{gamma} response, and an activated dendritic cell signature/M1 macrophage signature upon Dectin-1 stimulation. Dectin-1 stimulation induced a strong upregulation of MTORC1 signaling in all cohorts, although increased in the HIV-Older cohort (stimulation and baseline). Overall, our study demonstrates that the HIV Aging population has a distinct immune signature in response to Dectin-1 stimulation. This signature may contribute to the pro-inflammatory environment that is associated with HIV and Aging.

immunology↗

bioRxiv2022

Asymmetric Reconstruction of the Aquareovirus Core at Near-Atomic Resolution and Mechanism of Transcriptional Initiation

The Reoviridae family of dsRNA viruses is characterized by its members capacity for endogenous transcription of their multipartite genomes within proteinaceous capsids of 1 to 3 layers. These viruses share inner core particles (ICPs) that conform to icosahedral, T=2*, symmetry, but differ in two major respects: first, the presence or absence of RNA-capping turrets at each icosahedral vertex; second, the number of additional host-specific capsid layers that are often lost upon cell entry. While the role of these additional layers in host infection is generally understood, the absence of asymmetric ICP structures from turreted, multilayered reoviruses has obfuscated our understanding of how successive removal of these external layers impact the structural organization of the ICP and transcription initiation. Here, we present the 3.3 [A] resolution structure of the aquareovirus (ARV) ICP, and atomic models of the capsid proteins VP3 and VP6, transcriptional enzymatic complex (TEC) subunits VP2 and VP4, and RNA-capping turret protein VP1. These structures reveal significant differences when compared to those of the coated ARV, as well as their counterparts in single-layered cytoplasmic polyhedrosis virus (CPV). Compared to the double-layered ARV virion and infectious subvirion particle structures, the ARV ICP undergoes significant capsid expansion and widening of the nucleotide processing channels in its TEC and turret. Thus, the loss of outer capsid layers may regulate transcription initiation in ARV, unlike CPV which relies solely on allosteric regulation by binding transcriptional cofactors. These results shed new light on the mechanism of transcription initiation amongst turreted, multilayered members of Reoviridae.

molecular biology↗

bioRxiv2022

FAVOR: Functional Annotation of Variants Online Resource and Annotator for Variation across the Human Genome

Large-scale whole genome sequencing (WGS) studies and biobanks are rapidly generating a multitude of coding and non-coding variants. They provide an unprecedented resource for illuminating the genetic basis of human diseases. Variant functional annotations play a critical role in WGS analysis, result interpretation, and prioritization of disease- or trait-associated causal variants. Existing functional annotation databases have limited scope to perform online queries or are unable to functionally annotate the genotype data of large WGS studies and biobanks for downstream analysis. We develop the Functional Annotation of Variants Online Resources (FAVOR) to meet these pressing needs. FAVOR provides a comprehensive online multi-faceted portal with summarization and visualization of all possible 9 billion single nucleotide variants (SNVs) across the genome, and allows for rapid variant-, gene-, and region-level online queries. It integrates variant functional information from multiple sources to describe the functional characteristics of variants and facilitates prioritizing plausible causal variants influencing human phenotypes. Furthermore, a scalable annotation tool, FAVORannotator, is provided for functionally annotating and efficiently storing the genotype and variant functional annotation data of a large-scale sequencing study in an annotated GDS file format to facilitate downstream analysis. FAVOR and FAVORannotator are available at https://favor.genohub.org.

genetics↗

bioRxiv2022

Discovery, Structure, and Function of Filamentous 3-Methylcrotonyl-CoA Carboxylase

3-methylcrotonyl-CoA carboxylase (MCC) is a biotin-dependent enzyme necessary for leucine catabolism in most organisms. While the crystal structure of recombinant bacterial MCC has been characterized, the structure and potential polymerization of native MCC remain elusive. Here, we discovered that native MCC from Leishmania tarentolae (LtMCC) forms filaments and determined its structure at near-atomic resolution using cryoEM. 6{beta}6 LtMCC dodecamers assemble in a twisted-stacks architecture, manifesting as supramolecular rods extending up to approximately 400 nanometers. LtMCCs in filaments bind biotin but are not covalently biotinylated and lack coenzyme A. Filaments elongate by stacking 6{beta}6 LtMCCs onto the exterior -trimer of the terminal 6{beta}6 dodecamer. This stacking immobilizes the biotin carboxylase domains, sequestering the enzyme in an inactive state within the mitochondrial matrix. Our results support a new model for LtMCC catalysis, termed the dual-swinging-domains model, and cast new light on the functional significance of polymerization in the carboxylase superfamily and beyond.

molecular biology↗

bioRxiv2022

Inflammatory bowel disease-associated gut commensals degrade components of the extracellular matrix

Extracellular matrix (ECM) remodeling has emerged as a key feature of inflammatory bowel disease (IBD), and ECM fragments have been proposed as markers of clinical disease severity. Recent studies report increased protease activity in the gut microbiota of IBD patients. Nonetheless, the relationship between gut microbiota and ECM remodeling has remained unexplored. We hypothesized that members of the human gut microbiome can degrade host ECM, and that bacteria-driven remodeling, in turn, can enhance colonic inflammation. Through a variety of in vitro assays, we first confirmed that multiple bacterial species found in the human gut are capable of degrading specific ECM components. Clinical stool samples obtained from ulcerative colitis patients also exhibited higher levels of proteolytic activity in vitro compared to those of their healthy counterparts. Furthermore, culture supernatants from bacteria species capable of degrading human ECM accelerated inflammation in a dextran sodium sulfate (DSS)-induced colitis. Finally, we identified several of the bacterial proteases and carbohydrate degrading enzymes (CAZymes) potentially responsible for ECM degradation in vitro. Some of these protease families and CAZymes were also found in increased abundance in a metagenomic cohort of IBD. These results demonstrate that some commensal bacteria in the gut are indeed capable of degrading components of human ECM in vitro and suggest this proteolytic activity may be involved in the progression of IBD. A better understanding of the relationship between nonpathogenic gut microbes, host ECM, and inflammation could be crucial to unravel some of the mechanisms underlying host-bacteria interactions in IBD and beyond.

microbiology↗

bioRxiv2022

Detecting boolean asymmetric relationships with a loop counting technique and its implications for analyzing heterogeneity within gene expression datasets

Many traditional methods for analyzing gene-gene relationships focus on positive and negative correlations, both of which are a kind of symmetric relationship. Biclustering is one such technique that typically searches for subsets of genes exhibiting correlated expression among a subset of samples. However, genes can also exhibit asymmetric relationships, such as if-then relationships used in boolean circuits. In this paper we develop a very general method that can be used to detect biclusters within gene-expression data that involve subsets of genes which are enriched for these boolean-asymmetric relationships (BARs). These BAR-biclusters can correspond to heterogeneity that is driven by asymmetric gene-gene interactions, e.g., reflecting regulatory effects of one gene on another, rather than more standard symmetric interactions. Unlike typical approaches that search for BARs across the entire population, BAR-biclusters can detect asymmetric interactions that only occur among a subset of samples. We apply our method to a single-cell RNA-sequencing data-set, demonstrating that the statistically-significant BAR-biclusters indeed contain additional information not present within the more traditional boolean-symmetric-biclusters. For example, the BAR-biclusters involve different subsets of cells, and highlight different gene-pathways within the data-set. Moreover, by combining the boolean-asymmetric- and boolean-symmetric-signals, one can build linear classifiers which outperform those built using only traditional boolean-symmetric signals.

bioinformatics↗

bioRxiv2022

A comprehensive prediction of transcript isoforms in 19 chicken tissues by Oxford Nanopore long-read sequencing

To comprehensively identify and annotate transcript isoforms in the chicken genome, we generated Nanopore long-read sequencing data from a diverse set of 19 chicken tissues comprising 68 samples collected from experimental line 6 x line 7 F1 adult males and females. More than 23.8 million reads with mean read length of 790 bases and average quality of 18.2 were generated. The annotation and subsequent filtering resulted in identification of 55,382 transcripts with mean length of 1,700 bases at 40,547 loci, representing [~]1.4 transcripts per locus. Among them, we predicted 30,967 potential coding transcripts at 19,461 loci and 16,495 potential lncRNA transcripts at 15,512 loci. Compared to reference annotations, we found 52% of annotated transcripts could partially to fully match while 47% were novel and potentially transcribed from lncRNA loci. Based on our annotation, we quantified transcript expression across tissues and found brain tissues (i.e. cerebellum, cortex) expressed highest number of transcripts and loci. The further tissue specificity revealed that [~]22% of the transcripts displaying tissue specificity. Of them, the reproductive tissues (i.e. testis, ovary) contained the most tissue-specific transcripts. Despite sequencing 68 transcriptomes derived from 19 tissues, still [~]20% of Ensembl reference loci were not detected. This suggests that including additional samples from different cell types, developmental and physiological conditions, is needed to fully annotate the chicken genome. The application of Nanopore sequencing transcriptomes in this study demonstrated the usefulness of long-read data in discovering additional novel loci (e.g., lncRNA loci) and resolving complex transcripts (e.g., the longest transcript for the TTN locus).

genomics↗

bioRxiv2022

Multi-omics analyses identify transcription factor interplay in corneal epithelial fate determination and disease

The transparent corneal epithelium in the eye is maintained through the homeostasis regulated by limbal stem cells, while the non-transparent epidermis relies on epidermal keratinocytes for renewal. Despite their cellular similarities, the precise cell fates of these two types of epithelial stem cells, which give rise to functionally distinct epithelia, remain unknown. We performed a multi-omics analysis of human limbal stem cells from the cornea and keratinocytes from the epidermis, and characterized their molecular signatures, highlighting their similarities and differences. Through gene regulatory network analyses, we identified shared and cell type-specific transcription factors that define specific cell fates, and established their regulatory hierarchy. Single-cell RNA-seq analyses of the cornea and the epidermis confirmed these shared and cell type-specific transcription factors. Notably, the shared and limbal stem cell-specific transcription factors can cooperatively target genes associated with corneal opacity. Importantly, we discovered that FOSL2, a direct PAX6 target gene, is a novel candidate associated with corneal opacity, and it regulates genes implicated in corneal diseases. By characterizing molecular signatures, our study unveils the regulatory circuitry governing the limbal stem cell fate and its association with corneal opacity.

developmental biology↗

bioRxiv2022

Bioorthogonal in-cell Labeling and Profiling of N6-isopentenyladenosine (i6A) Modified RNA

Chemical modifications in RNAs play critical roles in structural diversification and functional regulation of many vital biochemical processes. Several hydrophobic prenyl-modifications have been discovered in a variety of RNA species since the 1990s. Prenyl groups are the feedstocks of terpene and many other biological molecules and the processes of prenylation in different macromolecules have been widely studied. We present here a new chemical biology technique to identify and label i6A, a prenyl-modified RNA residue, based on the unique reactivity of the prenyl group. We also found that iodine-mediated cycloaddition reactions of the prenyl group occurs in a superfast manner, and converts i6A from a hydrogen-bond acceptor into a donor. Based on this reactivity, we developed an iodine-mediated oxidation and reverse transcription (IMORT) method to profile cellular i6A residues with a single-base resolution, allowing for the transcriptome-wide detection and analysis of various i6A-containing RNA species.

biochemistry↗

bioRxiv2022

ZmEREB57 regulates OPDA synthesis and enhances salt stress tolerance through two distinct signal pathways in Zea mays

In plants, APETALA2/Ethylene-Responsive Factor (AP2/ERF)-domain transcription factors play important roles in regulating responses to biotic and abiotic types of stress. In this study, a novel AP2/ERF gene in maize, ethylene responsive element binding factor 57 (ZmEREB57), was identified by comparative transcriptomics, which was significantly upregulated under salt treatment; however, its function remained unclear. Our findings revealed that ZmEREB57 is a nuclear protein with transactivation activity, induced by a number of abiotic types of stress. Whats more, two CRISPR/Cas9 knockout lines of ZmEREB57 conferred sensitivity to saline conditions. DNA affinity purification sequencing (DAP-Seq) analysis revealed that ZmEREB57 mainly binds to promoters containing the O-box like motif (CCGGCC) to regulate the expression of its target genes. Further experiments validated that ZmEREB57 directly bind to the promoter of ZmAOC2 involved in the synthesis of 12-oxo-phytodienoic acid (OPDA) and JA. Besides, transcriptome analysis identified a number of genes responded to both OPDA and JA treatment, while a different set of genes specifically responded specifically to OPDA, but not JA. Analysis of mutants deficient in the biosynthesis of OPDA and JA revealed that OPDA functions as a signaling molecule in the salt response. Our results provide evidence for ZmEREB57s involvement in salt tolerance by regulating OPDA and JA signaling, and confirm early observations that OPDA signaling can function independently of JA signaling in maize.

plant biology↗

bioRxiv2022

Targeted delivery of interferon-gamma by synNotch T cells sensitizes neuroblastoma cells to T cell-mediated killing

Downregulation of HLA is one of the most common tumor escape mechanisms by enabling tumors to persist in the presence of tumor-reactive T cells. HLA loss is particularly common in children with high-risk neuroblastoma, who have a 50% long-term survival despite dose-intensive regimens. We have now developed an approach for the targeted induction of HLA to restore sensitivity of neuroblastoma cells to T cell-mediated killing. Using synNotch technology, we have generated T cells that, upon binding of the neuroblastoma surface antigen GD2, secrete IFN-{gamma} without conferring direct cytotoxic activity (snGD2i). Treatment with snGD2i cells induces high and durable expression of HLA on neuroblastoma cells in vitro and in vivo and restores sensitivity to TCR-transgenic T cells targeting neuroblastoma-specific antigens. In contrast, treatment does not lead to upregulation of immune checkpoints or systemically increased levels of IFN-{gamma}. Targeted delivery of IFN-{gamma} using snGD2i cells is a promising new strategy to address immune escape in neuroblastoma. STATEMENT OF SIGNIFICANCEHLA loss remains one of the most common and unsolved immune escape mechanisms in cancer cells. We have now developed a cell-based approach for the targeted upregulation of HLA on tumor cells, which efficiently sensitizes the malignant cells to killing by tumor-reactive T cells.

bioengineering↗

bioRxiv2022

Comparative genomic insights into the evolution of Halobacteria-associated "Candidatus Nanohaloarchaeota"

The phylum "Candidatus Nanohaloarchaeota" is a representative halophilic lineage within DPANN superphylum. They are characterized by their nanosized cells and symbiotic lifestyle with Halobacteria. However, the development of the symbiosis remains unclear for the lack of genomes located at the transition stage. Here, we performed a comparative genomic analysis of "Ca. Nanohaloarchaeota". We propose a novel family "Candidatus Nanoanaerosalinaceae" represented by five de-replicated metagenome-assembled genomes obtained from hypersaline sediments and the enrichment cultures of soda-saline lakes. Phylogeny analysis reveals that the novel family are placed at the root of the family "Candidatus Nanosalinaceae" including the well-researched taxa. Most members of "Ca. Nanoanaerosalinaceae" contain lower proportion of putative horizontal gene transfers from Halobacteria than "Ca. Nanosalinaceae", while they maintain moderately acidic proteomes for hypersaline adaptation of "salt-in" strategy, suggesting that "Ca. Nanoanaerosalinaceae" have not established an intimate association with Halobacteria, and may descend from an intermediate stage. Functional prediction discloses that they exhibit divergent potentials in carbohydrate and organic acids metabolism, and environmental responses. Historical events reconstruction illustrates that the involved genes acquired at the putative ancestors possibly drive the evolutionary and symbiotic divergences. Globally, this research on the new family "Ca. Nanoanaerosalinaceae" enriches the taxonomic and functional diversity of "Ca. Nanohaloarchaeota", and provides insights into the evolutionary process of "Ca. Nanohaloarchaeota" and their Halobacteria-associated symbiosis. ImportanceDPANN superphylum is a group of archaea widely distributing in various habitats. They generally have small cells, and perform a symbiotic lifestyle with other archaea. The archaeal symbiotic interaction is important to understand microbial community. However, the formation and evolution of the symbiosis between the DPANN lineages and other diverse archaea remain unclear. Based on phylogeny, hypersaline adaptation, functional potentials, and historical events of "Ca. Nanohaloarchaeota", a representative phylum within the DPANN superphylum, we report a novel family descending from an intermediate stage, and we illustrate the evolutionary process of "Ca. Nanohaloarchaeota" and their Halobacteria-associated symbiosis. Furthermore, we find the acquired genes involved in carbohydrate and organic acids metabolism and environmental responses possibly drive the evolutionary and symbiotic divergences. Altogether, this research helps in understanding the evolution of the archaeal symbiosis, and provides a model for the evolution of the other DPANN lineages.

microbiology↗

bioRxiv2022

Nature-Inspired Chemical Probes for in-cell Labeling of Lipidized RNA and Identification of New Regulatory Enzymes

RNA modifications play pivotal roles in numerous cellular processes and human diseases. In addition to well-studied methyl-based modifications, hydrophobic prenyl-modifications have also been found in many RNA species. Here we report two chemical labeling strategies for tagging lipid-modified RNAs by taking advantage of a natural SelU-mediated tRNA geranylation process and the special reactivity of prenyl-groups. We synthesized a series of clickable geranyl-pyrophosphate analogs and identified two candidates for indirect RNA labeling using a two-step process, azidation-and-click-tagging of fluorescent dyes, namely ACT-Flu. We also developed a direct metabolic incorporation and biorthogonal tagging (MIBT-Tag) method based on the Ene-ligation of prenyl-groups. Both methods have been successfully applied to in-cell RNA labeling and the identification of new proteins associated with the geranylation process through proteomic and bioinformatic studies. These biochemical toolsets enable further in vivo applications to study prenylation pathways and monitor their status in both healthy and diseased cells.

biochemistry↗

bioRxiv2022

A Unified Catalog of 19,251 Non-human Reference Species Genomes Provides New Insights into the Mammalian Gut Microbiomes

The gut microbiota is essential for host health and survival. Here, using samples from animals living in the Qinghai-Tibetan Plateau, we recovered 119,568 metagenome-assembled genomes (MAGs) that were clustered into 19,251 species-level genome bins (SGBs) of which most represent novel species. We present a novel mechanism shaping mammalian gut microbiomes using ancestral founder bacteria (AFB) as a core skeleton and recurring lineage-specific gains of microbial species that are transferred frequently among multiple hosts, not strictly limited by host phylogeny. Such lineage specific gains are responsible for increasing gut microbial diversity, maintaining functional stability, and endowing specific functions for host adaptions. Our analyses did not support the existence of co-phylogeny or co-speciation events between mammal hosts and their individual gut symbionts. The results presented in this study not only reveal novel unique gut microbial species and offer insight of value for understanding the diversity, stability, functionality of the mammalian gut microbiomes, and the co-evolution with their hosts, but also emphasize that animals living in extreme environments are a promising resource for the discovery of novel biological functions.

microbiology↗

bioRxiv2022

Preclinical evaluation of RQ3013, a broad-spectrum mRNA vaccine against SARS-CoV-2 variants

The global emergence of SARS-CoV-2 variants has led to increasing breakthrough infections in vaccinated populations, calling for an urgent need to develop more effective and broad-spectrum vaccines to combat COVID-19. Here we report the preclinical development of RQ3013, an mRNA vaccine candidate intended to bring broad protection against SARS-CoV-2 variants of concern (VOCs). RQ3013, which contains pseudouridine-modified mRNAs formulated in lipid nanoparticles, encodes the spike(S) protein harboring a combination of mutations responsible for immune evasion of VOCs. Here we characterized the expressed S immunogen and evaluated the immunogenicity, efficacy, and safety of RQ3013 in various animal models. RQ3013 elicited robust immune responses in mice, hamsters, and nonhuman primates (NHP). It can induce high titers of antibodies with broad cross-neutralizing ability against the Wild-type, B.1.1.7, B.1.351, B.1.617.2, and the omicron B.1.1.529 variants. In mice and NHP, two doses of RQ3013 protected the upper and lower respiratory tract against infection by SARS-CoV-2 and its variants. We also proved the safety of RQ3013 in NHP models. Our results provided key support for the evaluation of RQ3013 in clinical trials.

immunology↗

bioRxiv2022

Atomic model of Vesicular Stomatitis Virus and Mechanism of Assembly

Like other negative-strand RNA viruses (NSVs) such as influenza and rabies, vesicular stomatitis virus (VSV) has a three-layered organization: a layer of matrix protein (M) resides between the membrane envelope, studded by glycoprotein (G), and the nucleocapsid, composed of the nucleocapsid protein (N) and the encapsidated genomic RNA. Lack of in situ atomic structures of these viral components has limited our understanding of the virion assembly mechanism. Here, by cryoEM and sub-particle reconstruction, we have determined the in situ structures of M and N inside VSV at 3.47 [A] resolution. In the virion, N and M have a stoichiometry of 1:2. The in situ structures of both N and M differ from their crystal structures in their N-terminal segments and oligomerization loops. N-RNA, N-N, and N-M-M interactions govern the formation of the capsid. A double layer of M contributes to packaging of the helical nucleocapsid: the inner M (IM) joins neighboring turns of the N helix, while the outer M (OM) contacts G and the membrane envelope. The pseudo-crystalline organization of G is further mapped by cryoET. The mechanism of VSV assembly is delineated by the network interactions of these viral components.

biochemistry↗

bioRxiv2022

TME induced TRAIL secretion from engineered macrophages for anti-tumor therapy

Capacity of tumor niche chemotaxis and long-term persistency making macrophage as great vehicles for anti-tumor factor delivery. Macrophages-based delivery of chemokines or cytokines have been tested for tissue homeostasis and cancer repression. TRAIL as a promising anti-tumor cytokine, made little clinical progress due to limited stability and off-target toxicity. Here we engineered macrophages with tumor micro-environment (TME)-induced trimerized CP1-TRAIL secretion under the TME specific promoter Arg1 (Tri-TRAIL-iM). The Tri-TRAIL-iM cells displayed high specific inducible activity in both cell-based co-culture assay and in tumor baring mice models. Compared to normal TRAIL over-expressed macrophages under none-inducible promoter, Tri-TRAIL-iM infiltrated to tumor sites and showed superior apoptosis induction of cancer cells and tumor growth repression as well as less systemic side effect. This inducible delivery TRAIL strategy can be effectively further applied in clinical studies and can be coupled with other engineered methods to maximize the therapeutic outcomes for solid tumors.

cancer biology↗

bioRxiv2022

Structures and comparison of endogenous 2-oxoglutarate and pyruvate dehydrogenase complexes from bovine kidney

The -keto acid dehydrogenase complex family catalyzes the essential oxidative decarboxylation of -keto acids to yield acyl-CoA and NADH. Despite performing the same overarching reaction, members of the family have different component structures and structural organization between each other and across phylogenetic species. While native structures of -keto acid dehydrogenase complexes from bacteria and fungi became available recently, the atomic structure and organization of their mammalian counterparts in their native states remain unknown. Here, we report the cryo electron microscopy (cryoEM) structures of the endogenous cubic 2-oxoglutarate dehydrogenase complex (OGDC) and icosahedral pyruvate dehydrogenase complex (PDC) cores from bovine kidney determined at 3.5 [A] and 3.8 [A] resolution, respectively. The structures of multiple protein were reconstructed from a single lysate sample, allowing direct structural comparison without the concerns of differences arising from sample preparation and structure determination. Although native and recombinant E2 core scaffold structures are similar, native structures are decorated with their peripheral E1 and E3 subunits. Asymmetric sub-particle reconstructions support heterogeneity in the arrangements of these peripheral subunits. Additionally, despite sharing a similar monomeric fold, OGDC and PDC E2 cores have distinct interdomain and intertrimer interactions, which suggests a means of modulating self-assembly to mitigate heterologous binding between mismatched E2 species. The lipoyl moiety lies near a mobile gatekeeper within the interdomain active site of OGDC E2 and PDC E2. Analysis of the two-fold related intertrimer interface identified secondary structural differences and chemical interactions between icosahedral and cubic geometries of the core. Taken together, our study provides direct structural comparison of OGDC and PDC from the same source and offers new insights into determinants of interdomain interactions and of architecture diversity among -keto acid dehydrogenase complexes.

molecular biology↗