{"title":"The intricacies of tooth enamel: Embryonic origin, development and human genetics","authors":"Olivier Duverger, Janice S. Lee","doi":"10.1016/j.jsb.2024.108135","DOIUrl":"10.1016/j.jsb.2024.108135","url":null,"abstract":"<div><div>Tooth enamel is a fascinating tissue with exceptional biomechanical properties that allow it to last for a lifetime. In this mini review, we discuss the unique embryonic origin of this highly mineralized tissue, the complex differentiation process that leads to its “construction” (amelogenesis), and the various genetic conditions that lead to impaired enamel development in humans (amelogenesis imperfecta). Tremendous progress was made in the last 30 years in understanding the molecular and cellular mechanism that leads to normal and pathologic enamel development. However, several aspects of amelogenesis remain to be elucidated and the function of many genes associated with amelogenesis imperfecta still needs to be decoded.</div></div>","PeriodicalId":17074,"journal":{"name":"Journal of structural biology","volume":"216 4","pages":"Article 108135"},"PeriodicalIF":3.0,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142391448","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Maciej Nielipinski, Dominika Nielipinska, Agnieszka J. Pietrzyk-Brzezinska, Bartosz Sekula
{"title":"Arabidopsis thaliana argininosuccinate lyase structure uncovers the role of serine as the catalytic base","authors":"Maciej Nielipinski, Dominika Nielipinska, Agnieszka J. Pietrzyk-Brzezinska, Bartosz Sekula","doi":"10.1016/j.jsb.2024.108130","DOIUrl":"10.1016/j.jsb.2024.108130","url":null,"abstract":"<div><div>Arginine is an important amino acid in plants, as it not only plays a structural role and serves as nitrogen storage but is also a precursor for various molecules, including polyamines and proline. Arginine is produced by argininosuccinate lyase (ASL) which catalyzes the cleavage of argininosuccinate to arginine and fumarate. ASL belongs to the fumarate lyase family and while many members of this family were well-characterized, little is known about plant ASLs. Here we present the first crystal structures of ASL from the model plant, <em>Arabidopsis thaliana</em> (<em>At</em>ASL). One of the structures represents the unliganded form of the <em>At</em>ASL homotetramer. The other structure, obtained from a crystal soaked in argininosuccinate, accommodates the substrate or the reaction products in one of four active sites of the <em>At</em>ASL tetramer. Each active site is located at the interface of three neighboring protomers. The <em>At</em>ASL structure with ligands allowed us to analyze the enzyme-substrate and the enzyme-product interactions in detail. Furthermore, based on our analyses, we describe residues of <em>At</em>ASL crucial for catalysis. The structure of <em>At</em>ASL gives the rationale for the open-to-close transition of the GSS mobile loop and indicates the importance of serine 333 from this loop for the enzymatic action of the enzyme. Finally, we supplemented the structural data with the identification of sequence motifs characteristic for ASLs.</div></div>","PeriodicalId":17074,"journal":{"name":"Journal of structural biology","volume":"216 4","pages":"Article 108130"},"PeriodicalIF":3.0,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142391447","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yinghua Chen, Cassandra Villani, Amudha Ganapathy, Anne George
{"title":"Transcriptome profiling of DPP stimulated DPSCs identifies the role of autophagy in odontogenic differentiation","authors":"Yinghua Chen, Cassandra Villani, Amudha Ganapathy, Anne George","doi":"10.1016/j.jsb.2024.108134","DOIUrl":"10.1016/j.jsb.2024.108134","url":null,"abstract":"<div><div>Dentin phosphophoryn (DPP), synthesized and processed predominantly by the odontoblasts, serves both a structural and signaling role in dentin. In the ECM, DPP functions as an avid calcium and collagen binding protein and it also plays a crucial role as a scaffold for cell attachment and survival. The signaling function of DPP was demonstrated when undifferentiated mesenchymal cells stimulated with DPP, mediated calcium signaling through release of intracellular Ca<sup>2+</sup>. The objective of this study was to identify potentially novel signaling mechanisms that mediate odontoblast differentiation. Therefore, transcriptomes of DPSCs (dental pulp stem cells) with or without DPP stimulation were compared by bulk RNA-seq. Analysis of the unbiased RNA-seq data were subjected to functional enrichment analysis using Gene Ontology (GO) and KEGG pathways. Results identified several upregulated genes which were associated with autophagy, that were subsequently validated by RT-PCR. Western blotting analysis confirmed the up regulation of several autophagy markers such as ATG5, BECN1 and LC3A/B at specific time points. Autophagosome formation was also observed with DPP treatment. Additionally, autophagy supported a role for odontoblast differentiation of DPSCs. These findings suggest that DPP mediated autophagy might be a potential mechanism for the survival and terminal differentiation of DPSCs.</div></div>","PeriodicalId":17074,"journal":{"name":"Journal of structural biology","volume":"216 4","pages":"Article 108134"},"PeriodicalIF":3.0,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142400581","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Role of DMP1-mediated GRP78 activation in osteoimmunomodulation of periodontal ligament stem cells","authors":"Cassandra Villani, Yinghua Chen, Anne George","doi":"10.1016/j.jsb.2024.108133","DOIUrl":"10.1016/j.jsb.2024.108133","url":null,"abstract":"<div><div>The oral microbiome dysbiosis that causes periodontal disease leads to disruption of various signaling pathways that can result in alveolar bone degradation and subsequent tooth loss. Previous studies have demonstrated the potential of stem cell-based therapies in regeneration of the lost periodontium for the preservation of natural dentition. Periodontal ligament stem cells (PDLSCs) have osteoblast differentiation potential and their proximity to bone makes them an ideal candidate for regenerative therapies. Dentin matrix protein 1 (DMP1), a non-collagenous extracellular matrix protein, is integral to mineralized tissue formation due to its dual roles as an extracellular mediator of hydroxyapatite deposition and intracellular regulator of osteoblastogenesis. Heat shock protein 5A (GRP78) is a master regulator of the endoplasmic reticulum stress response and previous studies in our laboratory have also demonstrated its function as a membrane receptor for DMP1. Bulk RNA sequencing analysis of PDLSCs and PDLSCs overexpressing GRP78 (PDLSCs <em>GRP78</em>) with or without treatment with DMP1 was conducted to evaluate alterations to the differentially expressed gene profiles. This study aims to elucidate pathways in PDLSCs that are altered upon treatment with DMP1 to further characterize its relationship with GRP78 and cell stress signaling cascades. Pathway enrichment analysis of each transcriptomic profile demonstrated enrichment of osteogenic and immune response pathways upon DMP1 stimulation. Results from this study indicate a novel role for DMP1 and GRP78 in modulating immune signaling cascades in PDLSCs.</div></div>","PeriodicalId":17074,"journal":{"name":"Journal of structural biology","volume":"216 4","pages":"Article 108133"},"PeriodicalIF":3.0,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142400580","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The role of bone sialoprotein in bone healing","authors":"B.L. Foster","doi":"10.1016/j.jsb.2024.108132","DOIUrl":"10.1016/j.jsb.2024.108132","url":null,"abstract":"<div><div>Bone sialoprotein (BSP) is a multi-functional extracellular matrix (ECM) protein associated with mineralized tissues, particularly bone and cementum. The amino acid sequence of BSP includes three evolutionarily conserved sequences which contribute to functions of the protein: an N-terminal collagen-binding domain, polyglutamic acid (polyE) sequences involved in hydroxyapatite nucleation and crystal growth, and a C-terminal arginine-glycine-aspartic acid (RGD) integrin-binding domain. BSP promotes attachment and differentiation of osteogenic and osteoclastic cells. Genetic ablation of BSP in mice results in skeletal and dental developmental defects and impaired bone healing in both appendicular bone and alveolar bone of the jaw.</div><div>Several studies demonstrated positive effects of BSP on bone healing in rodent models, though other experiments show negligible results. Native (harvested from rat bones) BSP cross-linked to collagen induced slight improvements in calvarial bone healing in rats. Recombinant BSP and collagen delivered in a polylactide (PLA) cylinder improved bone defect healing in rat femurs. Both native and recombinant BSP delivered in a collagen gel improved alveolar bone healing in wild-type and BSP-deficient mice. These advances suggest BSP is a new player in bone healing that has potential to be an alternative or complimentary to other bioactive factors. Future studies are necessary to understand mechanisms of how BSP influences bone healing and optimize delivery and dose in different types of bone defects and injuries.</div></div>","PeriodicalId":17074,"journal":{"name":"Journal of structural biology","volume":"216 4","pages":"Article 108132"},"PeriodicalIF":3.0,"publicationDate":"2024-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142381098","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sebastian T. Mergelsberg , Hoshin Kim , Garry W. Buchko , Bojana Ginovska
{"title":"SAXS of murine amelogenin identifies a persistent dimeric species from pH 5.0 to 8.0","authors":"Sebastian T. Mergelsberg , Hoshin Kim , Garry W. Buchko , Bojana Ginovska","doi":"10.1016/j.jsb.2024.108131","DOIUrl":"10.1016/j.jsb.2024.108131","url":null,"abstract":"<div><div>Amelogenin is an intrinsically disordered protein essential to tooth enamel formation in mammals. Using advanced small angle X-ray scattering (SAXS) capabilities at synchrotrons and computational models, we revisited measuring the quaternary structure of murine amelogenin as a function of pH and phosphorylation at serine-16. The SAXS data shows that at the pH extremes, amelogenin exists as an extended monomer at pH 3.0 (R<sub>g</sub> = 38.4 Å) and nanospheres at pH 8.0 (R<sub>g</sub> = 84.0 Å), consistent with multiple previous observations. At pH 5.0 and above there was no evidence for a significant population of monomeric species. Instead, at pH 5.0, ∼80 % of the population is a heterogenous dimeric species that increases to ∼100 % at pH 5.5. The dimer population was observed at all pH > 5 conditions in dynamic equilibrium with a species in the pentamer range at pH < 6.5 and nanospheres at pH 8.0. At pH 8.0, ∼40 % of the amelogenin remained in the dimeric state. In general, serine-16 phosphorylation of amelogenin appears to modestly stabilize the population of the dimeric species.</div></div>","PeriodicalId":17074,"journal":{"name":"Journal of structural biology","volume":"216 4","pages":"Article 108131"},"PeriodicalIF":3.0,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142378031","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"On the abundance and importance of AXXXA sequence motifs in globular proteins and their involvement in CβCβ interaction","authors":"Surbhi Vilas Tajane , Abhilasha Thakur , Srijita Acharya , Pinak Chakrabarti , Sucharita Dey","doi":"10.1016/j.jsb.2024.108129","DOIUrl":"10.1016/j.jsb.2024.108129","url":null,"abstract":"<div><div>The AXXXA and GXXXG motifs are frequently observed in helices, especially in membrane proteins. The motif GXXXG is known to stabilize helix-helix association in membrane proteins via C<sub>α</sub>H<img>O bonding. AXXXA sequence motif additionally stabilizes the folded state of proteins. We found 27,000 and 18,000 occurrences of AXXXA and GXXXG motifs in a non-redundant set of 6000 obligate homodimeric (OD) complexes. Interestingly, this is less pronounced in transient homodimers (TD) and heterodimers (HetD). On average each obligate homodimer contains four AXXXA motifs, it is 2 and 3.5 for HetD and TD, respectively. Focusing on the binding surface it is seen that 27 % of the ODs contain at least one AXXXA motif at the interface, whereas it is 17 % and 15 % for HetD and TD respectively. AXXXA predominantly stabilizes the OD quaternary structure via the side chain C<sub>β</sub><img>C<sub>β</sub> interactions. This interaction is energetically favorable and is found to be a major driving force for OD quaternary structure stability. C<sub>β-</sub>C<sub>β</sub> interactions are observed ∼6 times higher than the known C<sub>α</sub>H<img>O interaction for helix-helix stabilization. Two additional new interactions of C<sub>β</sub><img>O and O<img>O are observed at the AXXXA containing interface regions. The occurrence of the motif gets drastically reduced if any of the terminal Ala residues are replaced by Gly. Our findings show the importance of AXXXA in providing stability to the quaternary structure through specific hydrophobic interactions and the specificity of the Ala residue at motif termini. The knowledge gained can be used for designing synthetic proteins of improved stability and for designing peptide-based therapeutics.</div></div>","PeriodicalId":17074,"journal":{"name":"Journal of structural biology","volume":"216 4","pages":"Article 108129"},"PeriodicalIF":3.0,"publicationDate":"2024-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142349012","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nadejda B. Matsko , Martin Schorb , Yannick Schwab
{"title":"Selective signal enhancement in Fourier space as a tool for discovering ultrastructural organization of macromolecules from in situ TEM","authors":"Nadejda B. Matsko , Martin Schorb , Yannick Schwab","doi":"10.1016/j.jsb.2024.108128","DOIUrl":"10.1016/j.jsb.2024.108128","url":null,"abstract":"<div><div>We present a Fourier transform (FT) based analytical method that allows to obtain of ultrastructural details from TEM images at sub-nanometer scale applying a selective filtering for singular macromolecule electron microscopy density information. It can be applied to high-pressure frozen, frozen hydrated and epoxy freeze substituted and embedded biological species. Both 2D projections and orthoslices from reconstructed tomograms can be used as a source of structural information. The key to the method is to select the macromolecule or organelle of interest with an accuracy of ≥ 7 – 3 nm (depending on pixel size of initial tilt series or singular image acquisition) and explore both the central low frequency FT intensity and diffraction regions to obtain the spatial structural organization and its dimensional characteristics, respectively. We also introduce a structure-specific selective mask FT filtering approach that can significantly improve image information even in poorly contrasted TEM of resin sections without heavy metal been used. The described method elucidates chromatin architecture without the need of averaging. A zigzag symmetry of 30 nm diameter chromatin fibers which in general is a controversial topic of research has been identified for <em>C. elegans</em> cells <em>in vivo</em> with sub-nanometer details being preserved in the images.</div></div>","PeriodicalId":17074,"journal":{"name":"Journal of structural biology","volume":"216 4","pages":"Article 108128"},"PeriodicalIF":3.0,"publicationDate":"2024-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142289841","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Three-dimensional cellular architecture of the sigmoid filament in Trichomonas vaginalis","authors":"Sharmila Ortiz , Raphael Verdan , Marlene Benchimol","doi":"10.1016/j.jsb.2024.108127","DOIUrl":"10.1016/j.jsb.2024.108127","url":null,"abstract":"<div><p><em>Trichomonas vaginalis</em> is a parasite protozoan that causes human trichomoniasis, a sexually transmitted infection (STI) that affects more than 156 million people worldwide. <em>T. vaginalis</em> contains an uncommon and complex cytoskeleton constituting the mastigont system, formed by several fibers and proteinaceous structures associated with basal bodies. Among these structures is the pelta-axostylar complex made of microtubules and striated filaments such as the costa and the parabasal filaments. In addition, some structures are poorly known and studied, such as the sigmoid filament and the X-filament. Here, we have isolated the <em>Trichomonas vaginalis</em> cytoskeleton and used UHR-SEM (ultra-high resolution scanning electron microscopy), tomography, immunofluorescence, immunolabeling, and backscattered electrons on SEM, negative staining to model the three-dimensional architecture and possible function of the sigmoid.</p></div>","PeriodicalId":17074,"journal":{"name":"Journal of structural biology","volume":"216 4","pages":"Article 108127"},"PeriodicalIF":3.0,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142145839","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Comparison of the global crystallographic texture of minerals in the shells of Bathymodiolus thermophilus Kenk et B.R. Wilson, 1985 and species of the genus Mytilus Linnaeus, 1758","authors":"Alexey Pakhnevich , Dmitry Nikolayev , Tatiana Lychagina","doi":"10.1016/j.jsb.2024.108126","DOIUrl":"10.1016/j.jsb.2024.108126","url":null,"abstract":"<div><p>The global crystallographic texture of calcite and aragonite in the shells of the bivalves <em>Bathymodiolus thermophilus</em>, <em>Mytilus galloprovincialis</em>, <em>M. edulis</em> and <em>M. trossulus</em> was studied by means of neutron diffraction. It was revealed that the general appearance of pole figures isolines of both minerals coincides for the studied species. The crystallographic texture sharpness evaluated by means of pole density on the calcite pole figures ((0006), <span><math><mrow><mo>(</mo><mn>10</mn><mover><mrow><mn>1</mn></mrow><mrow><mo>¯</mo></mrow></mover><mn>4</mn><mo>)</mo></mrow></math></span>) and aragonite pole figures ((012)/(121), (040)/(221)) coincides or has close values for deep-sea hydrothermal species <em>B. thermophilus</em> and the studied shallow-water species of the genus <em>Mytilus</em>. The calcite pole figures (0006) and <span><math><mrow><mo>(</mo><mn>10</mn><mover><mrow><mn>1</mn></mrow><mrow><mo>¯</mo></mrow></mover><mn>4</mn><mo>)</mo></mrow></math></span> of <em>B. thermophilus</em> show a shift in the position of texture maximum values compared to corresponding pole figures of other mussels. The shell microstructure of all studied mollusks is similar, only the shape of the fibers of <em>B. thermophilus</em> differs. Global crystallographic texture is a stable feature of the family Mytilidae. The extreme habitat conditions of the hydrothermal biotope do not significantly affect the crystallographic texture of <em>B. thermophilus</em>.</p></div>","PeriodicalId":17074,"journal":{"name":"Journal of structural biology","volume":"216 4","pages":"Article 108126"},"PeriodicalIF":3.0,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142145838","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}