Biology subjects

Inaba, K.

Publications and source records attributed to Inaba, K..

At least 19 recordsLinked to original sources

bioRxiv2026

KK-LC-1 reveals evolutionary divergence in the regulation of sperm motility between humans and mice

CT83 (KK-LC-1) is a cancer-testis antigen originally identified in human lung cancer cells and has recently attracted attention as a potential target for cancer therapy. Although KK-LC-1 orthologs have been identified in up to 160 animal species, a murine homolog had not previously been identified, hindering in vivo analysis of its physiological function. In this study, we identified the mouse homolog of KK-LC-1 and performed a comparative analysis of its properties in humans and mice, together with an investigation of its biological function using gene knockout (KO) mice. The murine Kk-lc-1 gene is located on the X chromosome and, like its human counterpart, contains an N-terminal transmembrane domain. In both humans and mice, KK-LC-1 is expressed specifically in the testis and localizes to the head and tail regions of sperm. Analysis of Kk-lc-1-deficient mice revealed normal spermatogenesis, and both male and female KO mice were fertile. However, sperm from Kk-lc-1-deficient males exhibited reduced motility caused by decreased flexibility of the midpiece and failed to penetrate the oocyte zona pellucida in vitro. This defect was rescued by artificial insemination using epididymal sperm, suggesting that maternal factors in vivo may compensate for reduced sperm motility. Although impaired sperm motility during in vitro fertilization (IVF) was rescued by murine Kk-lc-1, functional rescue by human KK-LC-1 was not observed. These findings indicate that KK-LC-1 contributes to sperm motility but is not essential for fertility. Moreover, species-specific differences in KK-LC-1-mediated regulation of sperm motility suggest functional divergence during evolution. The role of KK-LC-1 in sperm motility should therefore be considered in the clinical development of cancer therapies targeting KK-LC-1.

developmental biology↗

bioRxiv2026

Establishing genetically controlled, closed 1 colonies of an ascidian

Recent technological advances have made many "non-model" organisms accessible for experimental studies. However, reference inbred strains were not necessarily available, especially in marine invertebrates, and genetic background of organisms used for experiments are often non-uniform. This situation potentially affects experimental reproducibility. Although ascidians, Ciona intestinalis (type A, or C. robusta), are a widely used marine animal for many areas of experimental biology including developmental studies, no reference strains have been obtained despite extensive efforts. As an alternative way to improve reproducibility, we have established and maintained ascidian colonies through intra-population breeding every year from 2016 to 2020, and monitored genomic variants of these colonies. This method does not reduce genetic variations but instead manages and monitors genetic variations in the colonies, providing an easy and cost-effective way of increasing experimental reproducibility. Furthermore, we recently upgraded these genetically isolated, closed colonies that were re-established every year, and have maintained them for more than three years only through intra-population breeding and occasional back-cross using cryopreserved sperm. Genetic variants that we revealed using 3.7 tera-bases of sequence data will help to design future experiments in this species. Our data also show that two wild-populations, which were used to establish the colonies, have maintained distinct genetic backgrounds, although their habitats are directly linked to the Pacific Ocean and only 170 km apart. More importantly, genetic information regarding these colonies will undoubtedly improve experimental reproducibility and traceability, and our method will provide a realistic solution for performing reproducible experiments using non-model organisms.

developmental biology↗

bioRxiv2025

Spiral-Sensing and Fold-Change Detection Direct Ascidian Sperm to the Egg

From microorganisms to marine sperm, successful navigation toward chemical cues relies on the integration of sensory inputs with locomotion. Ascidian sperms exhibit a robust chemotactic strategy by swimming along circular paths whose centres form large-scale spirals, guiding them toward attractant-releasing eggs. Although their intracellular Ca2+ dynamics exhibit rhythmic bursts aligned with flagellar modulation, the underlying computational principles remain unclear. Here, we propose a minimal model that captures ascidian sperm chemotaxis through a combination of swimming trajectory control and an internal signalling model with fold-change detection (FCD). This model responds to relative rather than absolute changes in the stimulus concentration, achieving scale-invariant signal processing. Concurrently, the spiral swimming path enables spatial sampling of the concentration field, allowing the cell to infer gradient direction. Our findings demonstrate that the integration of a resilient signalling module and physically structured sampling trajectory enables effective chemotaxis in complex environments.

cell biology↗

bioRxiv2025

A cellular entity retaining only its replicative core: Hidden archaeal lineage with an ultra-reduced genome

Defining the minimal genetic requirements for cellular life remains a fundamental question in biology. Genomic exploration continually reveals novel microbial lineages, often exhibiting extreme genome reduction, particularly within symbiotic relationships. Here, we report the discovery of Candidatus Sukunaarchaeum mirabile, a novel archaeon with an unprecedentedly small genome of only 238 kbp --less than half the size of the smallest previously known archaeal genome-- from a dinoflagellate-associated microbial community. Phylogenetic analyses place Sukunaarchaeum as a deeply branching lineage within the tree of Archaea, representing a novel major branch distinct from established phyla. Environmental sequence data indicate that sequences closely related to Sukunaarchaeum form a diverse and previously overlooked clade in microbial surveys. Its genome is profoundly stripped-down, lacking virtually all recognizable metabolic pathways, and primarily encoding the machinery for its replicative core: DNA replication, transcription, and translation. This suggests an unprecedented level of metabolic dependence on a host, a condition that challenges the functional distinctions between minimal cellular life and viruses. The discovery of Sukunaarchaeum pushes the conventional boundaries of cellular life and highlights the vast unexplored biological novelty within microbial interactions, suggesting that further exploration of symbiotic systems may reveal even more extraordinary life forms, reshaping our understanding of cellular evolution. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=123 SRC="FIGDIR/small/651781v1_ufig1.gif" ALT="Figure 1"> View larger version (41K): org.highwire.dtl.DTLVardef@f5fbd6org.highwire.dtl.DTLVardef@168bee5org.highwire.dtl.DTLVardef@1ccb02forg.highwire.dtl.DTLVardef@14315fa_HPS_FORMAT_FIGEXP M_FIG C_FIG

evolutionary biology↗

bioRxiv2025

Unveiling novel signaling roles for human KDELR3 and KDELR1KDELRs Control AGR2 Biogenesis

KDEL receptors (KDELRs) prevent the secretion of soluble chaperones and enzymes meant to reside in the endoplasmic reticulum. While a single KDELR exists in yeast (ERD2), three variants are present in mammals, displaying high sequence similarity (73-83%). However, the phylogenetic conservation of the differences and the diverse tissue distribution of the three KDELRs suggest functional specialization. Here we show that, while all three receptors can prevent the secretion of KDEL-bearing clients, KDELR1 and KDELR3 regulate the production of AGR2, a key assistant of mucin folding, in opposite ways. AGR2 transcripts increase dramatically upon silencing KDELR3 but decrease when KDELR1 is downregulated. Silencing ERp44, but not other ER residents, phenocopies KDELR3 knockdown, suggesting that AGR2 regulation depends on ERp44-KDELR3 interactions. Our findings identify a novel regulatory circuit that controls the molecular composition of the early secretory pathway based on specific interactions between KDELRs and ER residents.

cell biology↗

bioRxiv2025

Isoform-specific patterns of phosphorylation on axonemal dynein heavy chains

Axonemal dyneins power ciliary motility and phosphorylation of key intermediate and light chain components affects the regulation and properties of these motors in very distantly related organisms. It is also known that many axonemal dynein heavy chains are subject to this post-translational modification although this has been little studied. Here we examine axonemal dynein heavy chains from a broad range of ciliated eukaryotes and identify phosphorylated sites embedded within various kinase recognition motifs such as those for PKA, PKC and casein kinase II. Mapping these sites onto discrete heavy chain types reveals class-specific locations apparently mediated by different kinases. For example, we find that all Chlamydomonas heavy chain phosphorylation sites are in an extended loop derived from AAA5 that arches over the coiled-coil buttress which in turn interacts with the microtubule-binding stalk. In contrast, most sites in the monomeric inner arm dyneins occur very close to the N-terminus and may be involved in assembly processes. In Chlamydomonas, the two cilia (termed cis and trans) exhibit different intrinsic beat frequencies and we identify cilium-specific phosphorylation patterns on both the heavy chain and outer arm docking complex consistent with differential regulation of these motors in the two organelles. SignificanceO_LIMany axonemal dynein heavy chains are extensively phosphorylated. However, the location, sequence context and potential role of these modifications is uncertain. C_LIO_LIHere we use mass spectrometry to define phosphorylated sites in inner and outer arm dyneins from a broad range of motile ciliated eukaryotes. C_LIO_LIWe identify numerous modified sites that correspond to various kinase consensus sequences and reveal that multiple sites occur in conserved locations depending on dynein heavy chain class. We also find phosphorylation modifications that are specific to either the cis or trans cilium of Chlamydomonas which may be related to their inherent beat frequency imbalance. C_LI

cell biology↗

bioRxiv2025

Drastic genome reduction driven by parasitic lifestyle: Two complete genomes of endosymbiotic bacteria possibly hosted by a dinoflagellate

Bacteria with endosymbiotic lifestyles often exhibit dramatic genome reduction. While the reduction of genomes in intracellular symbionts of animals, including parasitic bacteria, has been extensively studied, less is known about such bacteria associated with single-celled eukaryotes. Here, we report the genomes of two novel gammaproteobacterial lineages, RS3 and XS4, identified as putative parasitic endosymbionts of the dinoflagellate Citharistes regius. Phylogenetic analyses suggest that RS3 and XS4 belong to the family Fastidiosibacteraceae within the order Beggiatoales, forming independent lineages therein. The genomes of RS3 and XS4 are 529 Kbp and 436 Kbp in size, respectively, revealing drastic genome reduction compared to related bacterial genomes. XS4, which has a particularly reduced genome with low GC content, uses an alternative genetic code, in which UGA assigned tryptophan. The small genomes of RS3 and XS4 encode a limited number of proteins, retaining only approximately 20% of the predicted ancestral proteome. Metabolic reconstruction suggests that RS3 and XS4 are energy parasites, heavily dependent on their host for essential metabolites. Furthermore, we found that the ancestor of both genomes likely acquired an ADP:ATP antiporter gene via horizontal gene transfer, an event that may have enabled their evolution as energy parasites by facilitating the acquisition of ATP from their host. These observations on novel bacteria with highly reduced genomes expand our understanding of the phylogenetic and genomic diversity of endosymbiotic bacteria in protists.

evolutionary biology↗

bioRxiv2024

Apusomonad photophobic behavior highlights cytoskeletal responses to blue light in early eukaryotes

Light response is a fundamental characteristic of eukaryotic organisms, both unicellular and multicellular. However, no photoresponse has previously been reported in Apusomonadida, a group of small, free-living biflagellates phylogenetically positioned as a sister group to Opisthokonta (animals, fungi, and their unicellular relatives). Apusomonads are thus crucial for understanding the evolution of opisthokonts. Here, we report for the first time an avoidance response to blue light in the apusomonad Podomonas kaiyoae. This avoidance response is accompanied by an increase in gliding velocity, transient changes in flagellar waveforms, and alterations in cell shape. Dynamic cell contraction is induced by an increase in intracellular free Ca2+ and is inhibited by either a dynein inhibitor or an actin-disrupting drug. These findings suggest that the photophobic behavior of Podomonas kaiyoae relies on cytoskeletal responses mediated by both the dynein/tubulin and myosin/actin systems, which were acquired early in eukaryotic evolution. The dominance of the posterior flagellum in cilia-driven directional changes further supports the phylogenetic placement of apusomonads as a sister group to opisthokonts rather than other eukaryotic lineages.

evolutionary biology↗

bioRxiv2024

Ca2+-driven PDIA6 phase separation to ensure proinsulin quality control

The endoplasmic reticulum (ER) plays key roles in protein quality control1,2 and dynamic Ca2+ storage3,4 in eukaryotic cells. However, the protein homeostasis (proteostasis) system that regulates these ER functions is still incompletely characterised. Previous study revealed the importance of oligomerization in the function PDIA1, an ER-resident disulfide isomerase and molecular chaperone, regulates oligomeric states in accordance with client folding5. This result suggests that at least some of the 20 members of other PDI family may undergo regulated self-assembly in order to optimally function. Here, we show that Ca2+ triggers the phase separation of PDIA6 into liquid-like condensates. In contrast to the condensation mechanism observed for proteins containing low-complexity domains, our results indicate that transient but specific electrostatic interactions occur between the first and the third folded thioredoxin-like domains of PDIA6. We further show that the Ca2+-driven condensation of PDIA6 recruits PDIA3 and proinsulin, thus increasing their local concentrations. This process results in the 30-fold enhancement of proinsulin folding and in the inhibition of proinsulin aggregation. Our findings shed light on a condensation-driven Ca2+-mediated proteostasis cascade in the ER by revealing how the efficiency of the protein folding process can be enhanced within quality control granules.

biochemistry↗

bioRxiv2024

A sequential, RNA-derived, modified adenosine pathway safeguards cellular metabolism

RNA contains diverse post-transcriptional modifications and its catabolic breakdown yields numerous modified nucleosides that must be properly processed, but the molecular mechanism is largely unknown. Here, we show that three RNA-derived modified adenosines, N6-methyladenosine (m6A), N6,N6-dimethyladenosine (m6,6A), and N6-isopentenyladenosine (i6A), are sequentially metabolized to inosine monophosphate (IMP) to prevent their intrinsic cytotoxicity. These modified adenosines are phosphorylated by adenosine kinase (ADK) followed by adenosine deaminase-like (ADAL)-mediated deamination in both plants and animals. ADAL knockout mice accumulate N6-modified AMPs that allosterically inhibit AMP-activated protein kinase (AMPK), leading to dysregulation of glucose metabolism. Furthermore, ADK deficiency, reported in patients with severe metabolic defects, induces aberrant elevation of m6A/m6,6A/i6A, disrupting lipid metabolism and causing early death in mouse models. The findings unveil a fundamental mechanism by which cells alleviate the toxicity of modified adenosines, and that connects modified adenosines to human disease. In briefRNA catabolism yields diverse nucleosides with modifications attached. Three RNA-derived modified adenosines (m6A, m6,6A, and i6A) are intrinsically toxic and subjected to sequential metabolism to yield inosine monophosphate. Dysregulation of this pathway impairs energy balance and contributes to metabolic diseases. HighlightsO_LICytotoxic RNA catabolism-derived modified adenosines undergo sequential metabolism C_LIO_LIm6A, m6,6A, and i6A are phosphorylated by ADK then deaminated by ADAL to IMP C_LIO_LIm6AMP, m6,6AMP, and i6AMP allosterically inhibit AMP-mediated AMPK activation C_LIO_LILoss of ADK causes the accumulation of m6A, m6,6A, and i6A, and abnormal lipid metabolism, which can lead to genetic disease C_LI

cell biology↗

bioRxiv2024

Glutathione supersulphide regulates T-cell receptor signalling

Immunometabolism regulates functions and fates of immune cells including T cells. Supersulphides, which are universal metabolites containing catenated sulphur atoms, have various physiological functions based on their unique redox properties. Here we found that activation of T-cell receptor (TCR) signalling was accompanied by supersulphide decrease, which suggests a regulatory contribution of sulphur metabolism to immune function. Consistently, inhibiting supersulphide synthesis facilitated TCR activation and exacerbated allergen-induced type 2 inflammation in mice. Supplementation with glutathione trisulphide (GSSSG), a major endogenous supersulphide, suppressed TCR signalling in naive CD4+ T cells and their differentiation and effectively alleviated the inflammation. Docking simulation revealed interaction of GSSSG with CD3{varepsilon} chain in the TCR/CD3 complex, which was supported by mass spectrometry detection of persulphidated glutathionylation at a functionally important CXXC motif of CD3{varepsilon} chain. This study identified a new post-translational modification with supersulfides and demonstrated a critical contribution of sulphur metabolism to TCR signalling regulation.

biochemistry↗

bioRxiv2024

Convergent reductive evolution of cyanobacteria in symbiosis with Dinophysiales dinoflagellates

The diversity of marine cyanobacteria has been extensively studied due to their vital roles in ocean primary production. However, little is understood about the diversity of cyanobacterial species involved in symbiotic relationships. In this study, we successfully sequenced the complete genome of a cyanobacterium in symbiosis with Citharistes regius, a dinoflagellate species thriving in the open ocean. A phylogenomic analysis revealed that the cyanobacterium (CregCyn) belongs to the marine picocyanobacterial lineage, akin to another cyanobacterial symbiont (OmCyn) of a different dinoflagellate closely related to Citharistes. Nevertheless, these two symbionts are distinct lineages, suggesting independent origins of their symbiotic lifestyles. Despite the distinct origins, the genome analyses of CregCyn revealed shared characteristics with OmCyn, including an obligate symbiotic relationship with the host dinoflagellates and a degree of genome reduction. In contrast, a detailed analysis of genome subregions unveiled that the CregCyn genome carries genomic islands that are not found in the OmCyn genome. The presence of the genomic islands implies that exogenous genes have been integrated into the CregCyn genome at some point in its evolution. This study contributes to our understanding of the complex history of the symbiosis between dinoflagellates and cyanobacteria, as well as the genomic diversity of marine picocyanobacteria.

evolutionary biology↗

bioRxiv2023

Deciphering the Genomes of Motility-Deficient Mutants of Vibrio alginolyticus 138-2

The motility of Vibrio species plays a pivotal role in their survival and adaptation to diverse environments, and is intricately associated with pathogenicity in both humans and aquatic animals. Numerous mutant strains of Vibrio alginolyticus have been generated using UV or EMS mutagenesis to probe flagellar motility using molecular genetic approaches. Identifying these mutations promises to yield valuable insights into motility at the protein structural physiology level. In this study, we conducted an exhaustive analysis of the genomic structures of laboratory Vibrio strains that served as reference specimens. This assemblage notably encompassed the progenitor strain V. alginolyticus 138-2, alongside two strains displaying deficiencies in the lateral flagella (VIO5 and YM4) and one evincing a deficiency in the polar flagella (YM19). Subsequently, we meticulously ascertained the specific mutation sites within the 18 motility-deficient strains whose parents could be traced back to VIO5 or YM4. The identified mutations were conclusively localized within well-established flagella-related genes, providing a coherent rationale for the phenotypic traits exhibited by each motility-deficient mutant. In addition to these motility-related mutations, an average of 20 additional mutations was detected in each mutant strain. Genomic analysis of many mutants is a highly effective tool for comprehensively identifying genes related to specific phenotypes using forward genetics. IMPORTANCEBacteria of the Vibrio species rely on their motility for survival, adaptation, and pathogenicity. Identifying specific changes in the genome of non-motile mutants can help understand the genes that regulate flagella and motility in these bacteria. Herin, we sequenced the genome of Vibrio alginolyticus 138-2 strain and other motility defective strains and identified most of the mutations to be within genes encoding flagella. Additionally, we also provide a coherent rationale for the motility deficiency in these mutants. We believe that this study could provide a framework for genome sequencing-based methods for studying molecular functions in bacteria.

microbiology↗

bioRxiv2023

Structure of full-length ERGIC-53 in complex with MCFD2 for cargo transport

ERGIC-53 is a cargo receptor that promotes the transport of certain subsets of newly synthesized secretory proteins and membrane proteins from the endoplasmic reticulum (ER) to the Golgi apparatus (GA)1,2. Despite numerous structural and functional studies since its identification, the overall architecture and mechanism of action of this cargo receptor in its full-length form remain unclear. Here we present cryo-electron microscopy (cryo-EM) structures of full-length ERGIC-53 in complex with its functional partner MCFD2. These structures, in combination with SEC-MALS/SAXS analysis, reveal that ERGIC-53 exists as a homotetramer, not a homohexamer as previously suggested, and comprises a four-leaf clover-like head structure and a long stalk composed of three sets of four-helix coiled-coil followed by a transmembrane (TM) domain. The tetrameric head of ERGIC-53 consists of the vertically assembled carbohydrate recognition domains and the central four-helix coiled-coil. 3D variability analysis visualizes the globally flexible motion of the long stalk and local plasticity of the head region. Notably, MCFD2 has been found to possess a Zn2+ binding site in its N-terminal lid, which appears to modulate cargo binding. Altogether, unique mechanisms of regulated cargo capture and release by ERGIC-53 via the stalk bending and metal binding are proposed.

biochemistry↗

bioRxiv2023

Dose-response relationship for the resistance of human insulin to degradation by insulin-degrading enzyme

Deeper understanding of the mechanism of the action of insulin and insulin-degrading enzyme (IDE) is a central theme in research into physiology and the pathophysiology of type 2 diabetes mellitus. Despite significant progress regarding the substrate recruitment, unfolding, digestion, and release by IDE, the structure and function of the insulin hexamer during the degradation cycle of IDE remain to be fully characterized. In the present study, we have characterized the behavior of human insulin hexamer in the absence of zinc. Using cryo-electron microscopy, we also observed that these hexamers represented a structure similar to that of T6 insulin. More interestingly, we also observed complexes in which some of their monomeric insulin components are partially distorted at their hexametric symmetry. This ensures that insulin determines the kinetics of its degradation by IDE without the requirement for zinc. These findings provide new information regarding the molecular events in insulin assembly and disassembly that permit its selective digestion by IDE.

biochemistry↗

bioRxiv2022

"Two-story building" of a ctenophore comb plate provides structural and functional integrity for motility of giant multicilia

Comb plates (CPs) are large compound cilia uniquely seen in a basal metazoan group of ctenophores.1-3 Tens of thousands of cilia are bundled in a CP via structures connecting adjacent cilia, called compartmenting lamella (CL), which are the basis for the structural iridescent color and the coordination of ciliary movement of the CP.4-6 We previously reported the first component of CL, CTENO64, and found that it was convergently acquired in ctenophores and was essential for determination of ciliary orientation.3 However, CTENO64 is localized only in the proximal region of the CL; therefore, the molecular architecture of CL over the entire length has not been elucidated. Here, we identified a second CL component, CTENO189. This ctenophore-specific protein was present in the distal region of the CL, with a localization clearly segregated from CTENO64. Knockdown of the CTENO189 gene with morpholino antisense oligonucleotides resulted in complete loss of CLs in the distal region, but did not affect either the formation of CP or the orientation of each cilium. However, the hexagonal distribution of cilia was disarranged, and the metachronal coordination of CP along a comb row was lost in the CTENO189 morphants. The morphant CP showed asymmetric ciliary-type movement in normal seawater, and in a high-viscosity solution, it could not maintain the normal waveforms, becoming a symmetric flagellar-type. Our findings demonstrate a "two-story building" of CP, comprising the proximal CL, as the building foundation that rigidly fixes the ciliary orientation. The distal CL would reinforce the elastic connection among cilia to overcome the hydrodynamic drag of giant multiciliary plates.

cell biology↗

bioRxiv2022

Cryo-EM structures of human zinc transporter ZnT7 reveal the mechanism of Zn2+ uptake into the Golgi apparatus

Zinc ions (Zn2+) are vital to most cells, with the intracellular concentrations of Zn2+ being tightly regulated by multiple zinc transporters located at the plasma and organelle membranes. We herein present the 2.8-2.9 [A]-resolution cryo-EM structures of a Golgi-localized human Zn2+/H+ antiporter ZnT7 (hZnT7) in its outward- and inward-facing forms. Cryo-EM analyses showed that hZnT7 exists as a homodimer via tight interactions in both the cytosolic and transmembrane (TM) regions of two protomers, each of which contains a single Zn2+-binding site in its TM domain. hZnT7 undergoes a TM-helix rearrangement to create a negatively charged cytosolic cavity for Zn2+ entry in the inward-facing form and a widened luminal cavity for Zn2+ release in the outward-facing form. An exceptionally long cytosolic histidine-rich loop characteristic of hZnT7 can bind at least two Zn2+ ions, likely facilitating Zn2+ recruitment from the cytosol. Unique mechanisms of hZnT7-mediated Zn2+ uptake into the Golgi are proposed.

molecular biology↗

bioRxiv2021

Distinct roles and actions of PDI family enzymes in catalysis of nascent-chain disulfide formation

The mammalian endoplasmic reticulum (ER) harbors more than 20 members of the protein disulfide isomerase (PDI) family that act to maintain proteostasis. Herein, we developed an in vitro system for directly monitoring PDI- or ERp46-catalyzed disulfide bond formation in ribosome-associated nascent chains (RNC) of human serum albumin. The results indicated that ERp46 more efficiently introduced disulfide bonds into nascent chains with short segments exposed outside the ribosome exit site than PDI. Single-molecule analysis by high-speed atomic force microscopy further revealed that PDI binds nascent chains persistently, forming a stable face-to-face homodimer, whereas ERp46 binds for a shorter time in monomeric form, indicating their different mechanisms for substrate recognition and disulfide bond introduction. Similarly to ERp46, a PDI mutant with an occluded substrate-binding pocket displayed shorter-time RNC binding and higher efficiency in disulfide introduction than wild-type PDI. Altogether, ERp46 serves as a more potent disulfide introducer especially during the early stages of translation, whereas PDI can catalyze disulfide formation in RNC when longer nascent chains emerge out from ribosome.

biochemistry↗