Journal of structural biology最新文献_第2页

Mechanistic insights into cyclodextrins as substrates and inhibitors of GH57 family amylopullulanase from Aquifex aeolicus 环糊精作为水蛭GH57家族淀粉葡聚糖酶底物和抑制剂的机制研究。

IF 3 3区生物学

Journal of structural biology Pub Date : 2025-03-20 DOI: 10.1016/j.jsb.2025.108199

Zhimin Zhu , Minjun Li , Qin Xu , Liqing Huang , Huan Zhou , Weiwei Wang , Qisheng Wang , Feng Yu

{"title":"Mechanistic insights into cyclodextrins as substrates and inhibitors of GH57 family amylopullulanase from Aquifex aeolicus","authors":"Zhimin Zhu , Minjun Li , Qin Xu , Liqing Huang , Huan Zhou , Weiwei Wang , Qisheng Wang , Feng Yu","doi":"10.1016/j.jsb.2025.108199","DOIUrl":"10.1016/j.jsb.2025.108199","url":null,"abstract":"<div><div>Maltooligosaccharides (MOs) have gained significant attention in the food and pharmaceutical industries owing to their valuable functional properties, including controlled sweetness, digestibility, and enhanced bioavailability. However, conventional MOs is production involves complex processing steps and significant production costs. A potential high-efficiency synthesis of specific MOs can be achieved through the ring-opening reaction of cyclodextrins (CDs) catalyzed by amylolytic enzymes. In this study, we analyze the catalytic conversion of α-, β-, and γ-CDs by a GH57 family amylopullulanase from <em>Aquifex aeolicus</em> (AaApu) using thin-layer chromatography (TLC). Our findings demonstrate that AaApu has a substrate specificity for γ-CD, while all three CDs exert competitive inhibition on pullulan hydrolysis. To elucidate the molecular mechanism of CDs as inhibitor and substrate of amylopullulanase, we determined high-resolution crystal structures of AaApu (wild-type and D352N) in complex with α-, β-, and γ-CD through co-crystallization. These findings establish a structure–function framework for understanding the bifunctional nature of CDs as both substrates and inhibitors in GH57 amylopullulanases.</div></div>","PeriodicalId":17074,"journal":{"name":"Journal of structural biology","volume":"217 2","pages":"Article 108199"},"PeriodicalIF":3.0,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143692443","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}

引用次数: 0

Structural insights into the RNA binding inhibitors of the C-terminal domain of the SARS-CoV-2 nucleocapsid 对 SARS-CoV-2 核头壳 C 端结构的 RNA 结合抑制剂的结构研究。

IF 3 3区生物学

Journal of structural biology Pub Date : 2025-03-18 DOI: 10.1016/j.jsb.2025.108197

Preeti Dhaka, Jai Krishna Mahto, Ankur Singh, Pravindra Kumar, Shailly Tomar

{"title":"Structural insights into the RNA binding inhibitors of the C-terminal domain of the SARS-CoV-2 nucleocapsid","authors":"Preeti Dhaka, Jai Krishna Mahto, Ankur Singh, Pravindra Kumar, Shailly Tomar","doi":"10.1016/j.jsb.2025.108197","DOIUrl":"10.1016/j.jsb.2025.108197","url":null,"abstract":"<div><div>The SARS-CoV-2 nucleocapsid (N) protein is an essential structural element of the virion, playing a crucial role in enclosing the viral genome into a ribonucleoprotein (RNP) assembly, as well as viral replication and transmission. The C-terminal domain of the N-protein (N-CTD) is essential for encapsidation, contributing to the stabilization of the RNP complex. In a previous study, three inhibitors (ceftriaxone, cefuroxime, and ampicillin) were screened for their potential to disrupt the RNA packaging process by targeting the N-protein. However, the binding efficacy, mechanism of RNA binding inhibition, and molecular insights of binding with N-CTD remain unclear. In this study, we evaluated the binding efficacy of these inhibitors using isothermal titration calorimetry (ITC), revealing the affinity of ceftriaxone (18 ± 1.3 μM), cefuroxime (55 ± 4.2 μM), and ampicillin (28 ± 1.2 μM) with the N-CTD. Further inhibition assay and fluorescence polarisation assay demonstrated RNA binding inhibition, with IC<sub>50</sub> ranging from ∼ 12 to 18 μM and K<sub>D</sub> values between 24 μM to 32 μM for the inhibitors, respectively. Additionally, we also determined the inhibitor-bound complex crystal structures of N-CTD-Ceftriaxone (2.0 Å) and N-CTD-Ampicillin (2.2 Å), along with the structure of apo N-CTD (1.4 Å). These crystal structures revealed previously unobserved interaction sites involving residues K261, K266, R293, Q294, and W301 at the oligomerization interface and the predicted RNA-binding region of N-CTD. These findings provide valuable molecular insights into the inhibition of N-CTD, highlighting its potential as an underexplored but promising target for the development of novel antiviral agents against coronaviruses.</div></div>","PeriodicalId":17074,"journal":{"name":"Journal of structural biology","volume":"217 2","pages":"Article 108197"},"PeriodicalIF":3.0,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143669161","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}

引用次数: 0

Conformational landscape of the mycobacterial inosine 5′-monophosphate dehydrogenase octamerization interface 分枝杆菌肌苷5'-单磷酸脱氢酶八聚界面的构象景观。

IF 3 3区生物学

Journal of structural biology Pub Date : 2025-03-17 DOI: 10.1016/j.jsb.2025.108198

Ondřej Bulvas, Zdeněk Knejzlík, Anatolij Filimoněnko, Tomáš Kouba, Iva Pichová

{"title":"Conformational landscape of the mycobacterial inosine 5′-monophosphate dehydrogenase octamerization interface","authors":"Ondřej Bulvas, Zdeněk Knejzlík, Anatolij Filimoněnko, Tomáš Kouba, Iva Pichová","doi":"10.1016/j.jsb.2025.108198","DOIUrl":"10.1016/j.jsb.2025.108198","url":null,"abstract":"<div><div>Inosine 5′-monophosphate dehydrogenase (IMPDH), a key enzyme in bacterial purine metabolism, plays an essential role in the biosynthesis of guanine nucleotides and shows promise as a target for antimicrobial drug development. Despite its significance, the conformational dynamics and substrate-induced structural changes in bacterial IMPDH remain poorly understood, particularly with respect to its octameric assembly. Using cryo-EM, we present full-length structures of IMPDH from <em>Mycobacterium smegmatis</em> (<em>Msm</em>IMPDH) captured in a reaction intermediate state, revealing conformational changes upon substrate binding. The structures feature resolved flexible loops that coordinate the binding of the substrate, the cofactor, and the K<sup>+</sup> ion. Our structural analysis identifies a novel octamerization interface unique to <em>Msm</em>IMPDH. Additionally, a previously unobserved barrel-like density suggests potential self-interactions within the C-terminal regions, hinting at a regulatory mechanism tied to assembly and function of the enzyme. These data provide insights into substrate-induced conformational dynamics and novel interaction interfaces in <em>Msm</em>IMPDH, potentially informing the development of IMPDH-targeted drugs.</div></div>","PeriodicalId":17074,"journal":{"name":"Journal of structural biology","volume":"217 2","pages":"Article 108198"},"PeriodicalIF":3.0,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143663821","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}

引用次数: 0

Dengue virus-host interactions: Structural and mechanistic insights for future therapeutic strategies 登革病毒-宿主相互作用：未来治疗策略的结构和机制见解。

IF 3 3区生物学

Journal of structural biology Pub Date : 2025-03-14 DOI: 10.1016/j.jsb.2025.108196

Moumita Khanra , Indrani Ghosh , Samima Khatun , Nilanjan Ghosh , Shovanlal Gayen

{"title":"Dengue virus-host interactions: Structural and mechanistic insights for future therapeutic strategies","authors":"Moumita Khanra , Indrani Ghosh , Samima Khatun , Nilanjan Ghosh , Shovanlal Gayen","doi":"10.1016/j.jsb.2025.108196","DOIUrl":"10.1016/j.jsb.2025.108196","url":null,"abstract":"<div><div>Dengue pathogen, transmitted by mosquitoes, poses a growing threat as it is capable of inflicting severe illness in humans. Around 40% of the global population is currently affected by the virus, resulting in thousands of fatalities each year. The genetic blueprint of the virus comprises 10 proteins. Three proteins serve as structural components: the capsid (C), the precursor of the membrane protein (PrM/M), and the envelope protein (E). The other proteins serve as non-structural (NS) proteins, consisting of NS1, NS2A, NS2B, NS3, NS4A, NS4B, and NS5. The virus relies on these NS proteins to expropriate host proteins for its replication. During their intracellular replication, these viruses engage with numerous host components and exploit the cellular machinery for tasks such as entry into various organs, propagation, and transmission. This review explores mainly the relationship between dengue viral protein and host proteins elucidating the development of viral-host interactions. These relationships between the virus and the host give important information on the processes behind viral replication and the etiology of disease, which in turn facilitates the creation of more potent treatment strategies.</div></div>","PeriodicalId":17074,"journal":{"name":"Journal of structural biology","volume":"217 2","pages":"Article 108196"},"PeriodicalIF":3.0,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143639637","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}

引用次数: 0

NMR and semi-synthesis in synergy to study protein regulation 核磁共振和半合成协同研究蛋白质调控。

IF 3 3区生物学

Journal of structural biology Pub Date : 2025-03-13 DOI: 10.1016/j.jsb.2025.108192

Thibault Viennet

引用次数: 0

MRGPRX2 ligandome: Molecular simulations reveal three categories of ligand-receptor interactions MRGPRX2配体：分子模拟揭示了配体与受体相互作用的三种类型。

IF 3 3区生物学

Journal of structural biology Pub Date : 2025-03-12 DOI: 10.1016/j.jsb.2025.108193

Philip Maier , Moritz Macht , Silvan Beck , Pavel Kolkhir , Magda Babina , Andreas E. Kremer , Dirk Zahn , Katharina Wolf

{"title":"MRGPRX2 ligandome: Molecular simulations reveal three categories of ligand-receptor interactions","authors":"Philip Maier , Moritz Macht , Silvan Beck , Pavel Kolkhir , Magda Babina , Andreas E. Kremer , Dirk Zahn , Katharina Wolf","doi":"10.1016/j.jsb.2025.108193","DOIUrl":"10.1016/j.jsb.2025.108193","url":null,"abstract":"<div><h3>Introduction</h3><div>Mas-related G protein-coupled receptor (MRGPR) X2 is a mast cell receptor known to be activated by a wide range of ligands of various size, charge and origin. Our aim is to gain a deeper understanding of the binding processes of the different MRGPRX2 ligands and the ligand-receptor interactions in order to identify crucial structural elements for receptor activation.</div></div><div><h3>Materials and methods</h3><div>We used the three-dimensional structure of MRGPRX2 described in <em>Nature</em> in 2021 by Cao et al. and Yang et al. to computationally model the interaction between MRGPRX2 and small molecule ligands under simulated physiological conditions.</div></div><div><h3>Results</h3><div>Docking and post-docking samplings of the MRGPRX2 ligandome within the GPCR binding pocket led to the identification of key structural features for protein–ligand interactions. On the ligand side, we obtained an overlay of different molecular patterns or chemical groups by comparing different ligands plotted on the receptor. These key features include at least one protonated amine moiety of MRGPRX2 ligands contributing to one salt-bridge and one π-cation interaction, as well as an extended non-polar domain of the ligand surface that offer hydrophobic segregation and/or π-stacking interactions. In the receptor, we identified amino acids (GLU164, ASP184, PHE101, PHE170, TRP243, PHE244 and PHE257) that specifically interact via hydrogen bonding, salt-bridges, π-cation interactions and π-π stacking with the ligands to direct binding and ultimately receptor activation.</div></div><div><h3>Discussion</h3><div>Our insights into ligand-receptor interaction obtained by molecular modeling can help to predict mast cell activation via MRGPRX2 including adverse reactions, and facilitate the development of MRGPRX2 antagonists for the treatment of mast cell-mediated diseases.</div></div>","PeriodicalId":17074,"journal":{"name":"Journal of structural biology","volume":"217 2","pages":"Article 108193"},"PeriodicalIF":3.0,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143630507","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}

引用次数: 0

Allosteric inhibition of cytosolic NADP+-dependent isocitrate dehydrogenase by oxaloacetate 草酰乙酸对胞浆内NADP+依赖性异柠檬酸脱氢酶的变构抑制作用。

IF 3 3区生物学

Journal of structural biology Pub Date : 2025-03-08 DOI: 10.1016/j.jsb.2025.108183

Dong Kyu Kim , Ha Yeon Cho , Hyo Je Cho , Beom Sik Kang

{"title":"Allosteric inhibition of cytosolic NADP+-dependent isocitrate dehydrogenase by oxaloacetate","authors":"Dong Kyu Kim , Ha Yeon Cho , Hyo Je Cho , Beom Sik Kang","doi":"10.1016/j.jsb.2025.108183","DOIUrl":"10.1016/j.jsb.2025.108183","url":null,"abstract":"<div><div>NADP<sup>+</sup>-dependent cytosolic isocitrate dehydrogenase (IDH1) plays a crucial role in providing reducing energy in response to oxidative stress through the oxidative decarboxylation of isocitrate. NADPH generated by IDH1 serves as an essential cofactor for fatty acid synthesis. The regulation of IDH1 activity is vital for the biological functions of NADPH within cells, and mutations in IDH1 have been implicated in various cancers. In an effort to identify small regulatory molecules for IDH1, we determined the crystal structures of mouse IDH1 complexed with isocitrate and with oxaloacetate. Each IDH1 comprises large and small domains that form an active site, along with a clasp domain that connects two IDH1 molecules for dimerization. Isocitrate was located at the active site in the presence of a magnesium ion, while oxaloacetate was found at a novel site formed by the two clasp domains, in addition to the active site. The activity of IDH1 was diminished in the presence of oxaloacetate and could not be restored by the addition of isocitrate, indicating the presence of allosteric regulation. The activity of the IDH1 H170A mutant, which is unable to bind oxaloacetate in the clasp domain, was unaffected by oxaloacetate. This allosteric regulatory site may serve as a potential target for novel IDH1 inhibitors.</div></div>","PeriodicalId":17074,"journal":{"name":"Journal of structural biology","volume":"217 2","pages":"Article 108183"},"PeriodicalIF":3.0,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143597205","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}

引用次数: 0

Improving CryoEM maps of symmetry-mismatched macromolecular assemblies: A case study on the flagellar motor 改进对称错配大分子组装的低温电镜图谱：鞭毛马达的案例研究。

IF 3 3区生物学

Journal of structural biology Pub Date : 2025-03-05 DOI: 10.1016/j.jsb.2025.108184

Prashant K. Singh , T.M. Iverson

{"title":"Improving CryoEM maps of symmetry-mismatched macromolecular assemblies: A case study on the flagellar motor","authors":"Prashant K. Singh , T.M. Iverson","doi":"10.1016/j.jsb.2025.108184","DOIUrl":"10.1016/j.jsb.2025.108184","url":null,"abstract":"<div><div>Advances in cryo-electron microscopy instrumentation and sample preparation have significantly improved the ability to collect quality data for biomolecular structures. However, achieving resolutions consistent with data quality remains challenging in structures with symmetry mismatches. As a case study, the bacterial flagellar motor is a large complex essential for bacterial chemotaxis and virulence. This motor contains a smaller membrane-supramembrane ring (MS-ring) and a larger cytoplasmic ring (C-ring). These two features have a 33:34 symmetry mismatch when expressed in <em>E. coli</em>. Because close symmetry mismatches are the most difficult to deconvolute, this makes the flagellar motor an excellent model system to evaluate refinement strategies for symmetry mismatch. We compared the performance of masked refinement, local refinement, and particle subtracted refinement on the same data. We found that particle subtraction prior to refinement was critical for approaching the smaller MS-ring. Additional processing resulted in final resolutions of 3.1 Å for the MS-ring and 3.0 Å for the C-ring, which improves the resolution of the MS-ring by 0.3 Å and the resolution of the C-ring by 1.0 Å as compared to past work. Although particle subtraction is fairly well-established, it is rarely applied to problems of symmetry mismatch, making this case study a valuable demonstration of its utility in this context.</div></div>","PeriodicalId":17074,"journal":{"name":"Journal of structural biology","volume":"217 2","pages":"Article 108184"},"PeriodicalIF":3.0,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143585985","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}

引用次数: 0

Cryo-iCLEM: Cryo correlative light and electron microscopy with immersion objectives Cryo- iclem：带浸没物镜的低温相关光学和电子显微镜。

IF 3 3区生物学

Journal of structural biology Pub Date : 2025-03-01 DOI: 10.1016/j.jsb.2025.108179

Niko Faul , Shih-Ya Chen , Christian Lamberz , Mark Bruckner , Christian Dienemann , Thomas P. Burg

{"title":"Cryo-iCLEM: Cryo correlative light and electron microscopy with immersion objectives","authors":"Niko Faul , Shih-Ya Chen , Christian Lamberz , Mark Bruckner , Christian Dienemann , Thomas P. Burg","doi":"10.1016/j.jsb.2025.108179","DOIUrl":"10.1016/j.jsb.2025.108179","url":null,"abstract":"<div><div>Correlative light and electron microscopy (CLEM) is a powerful tool for investigating cellular structure and function at the molecular level. However, while electron microscopy is often performed to great advantage at cryogenic temperatures, this is not always the case for light microscopy. One key challenge is the lack of cryo-compatible immersion objectives. In recent years, multiple cryoimmersion light microscopy (cryo-iLM) approaches have been described, but these techniques have never been used in correlative approaches. Here we present a novel workflow for correlative cryoimmersion light microscopy and electron cryomicroscopy (cryo-iCLEM). Cryo-electron tomography conducted before and after cryo-iLM reveals that cryo-iCLEM maintains ultra-thin, electron-transparent samples mechanically intact and does not degrade the ultrastructural preservation achieved through plunge-freezing. For cryo-iLM, the sample is first embedded in a viscous immersion medium at cryogenic temperatures and examined with a custom cryo-immersion objective. After cryo-iLM, the immersion medium is dissolved in liquid ethane, allowing for subsequent cryo-EM imaging. We further show that cryo-iCLEM can be used on FIB-lamellae, demonstrating that mechanically sensitive samples remain undamaged. Embedding the sample in the immersion fluid reduces contamination and thus allows data acquisition over many hours. Samples can therefore be examined in detail with the advantage of low bleaching rates of fluorophores at cryogenic temperatures. In the future, we hope that our approach can help improve the performance of many advanced light microscopy techniques when they are applied in the context of cryo-CLEM.</div></div>","PeriodicalId":17074,"journal":{"name":"Journal of structural biology","volume":"217 1","pages":"Article 108179"},"PeriodicalIF":3.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143458330","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}

引用次数: 0

Lack of embryonic skeletal muscle in mice leads to abnormal mineral deposition and growth 小鼠胚胎骨骼肌缺乏导致异常的矿物质沉积和生长。

IF 3 3区生物学

Journal of structural biology Pub Date : 2025-03-01 DOI: 10.1016/j.jsb.2025.108178

Isabella Silva Barreto , Marianne Liebi , Sophie Le Cann , Saima Ahmed , Leonard C. Nielsen , Tilman A. Grünewald , Hector Dejea , Viviane Lutz-Bueno , Niamh C. Nowlan , Hanna Isaksson

{"title":"Lack of embryonic skeletal muscle in mice leads to abnormal mineral deposition and growth","authors":"Isabella Silva Barreto , Marianne Liebi , Sophie Le Cann , Saima Ahmed , Leonard C. Nielsen , Tilman A. Grünewald , Hector Dejea , Viviane Lutz-Bueno , Niamh C. Nowlan , Hanna Isaksson","doi":"10.1016/j.jsb.2025.108178","DOIUrl":"10.1016/j.jsb.2025.108178","url":null,"abstract":"<div><div>Developing bones can be severely impaired by a range of disorders where muscular loading is abnormal. Recent work has indicated that the effects of absent skeletal muscle on bones are more severe early in development, with rudiment length and mineralization lengths being almost normal in muscle-less limbs just prior to birth. However, the impact of abnormal mechanical loading on the nanoscale structure and composition during prenatal mineralization remains unknown. In this exploratory study, we characterized the mineralization process of humeri from muscle-less limb embryonic mice using a multiscale approach by combining X-ray scattering and fluorescence with infrared and light microscopy to identify potential key aspects of interest for future in-depth investigations. Muscle-less humeri were characterized by initially less mineralized tissue to later catch up with controls, and exhibited continuous growth of mineral particles, which ultimately led to seemingly larger mineral particles than their controls at the end of development. Muscle-less limbs exhibited an abnormal pattern of mineralization, reflected by a more widespread distribution of zinc and homogenous distribution of hydroxyapatite compared to controls, which instead showed trabecular-like structures and zinc localized only to regions of ongoing mineralization. The decrease in collagen content in the hypertrophic zone due to resorption of the cartilage collagen matrix was less distinct in muscle-less limbs compared to controls. Surprisingly, the nanoscale orientation of the mineral particles was unaffected by the lack of skeletal muscle. The identified accelerated progression of ossification in muscle-less limbs at later prenatal stages provides a possible anatomical mechanism underlying their recovery in skeletal development.</div></div>","PeriodicalId":17074,"journal":{"name":"Journal of structural biology","volume":"217 1","pages":"Article 108178"},"PeriodicalIF":3.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143433421","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}

引用次数: 0