Journal of Biological Chemistry最新文献_第8页

Redox potential tuning by calcium ions in a novel c-type cytochrome from an anammox organism. 钙离子在厌氧生物新型 c 型细胞色素中的氧化还原电位调节作用

IF 4 2区生物学

Journal of Biological Chemistry Pub Date : 2024-12-13 DOI: 10.1016/j.jbc.2024.108082

M Akram, D Hauser, A Dietl, M Steigleder, G M Ullmann, T R M Barends

引用次数: 0

Phosphorylation of Ephexin4 at Ser-41 contributes to chromosome alignment via RhoG activation in cell division. 细胞分裂过程中，Ephexin4在Ser-41处的磷酸化有助于通过RhoG激活染色体排列。

IF 4 2区生物学

Journal of Biological Chemistry Pub Date : 2024-12-13 DOI: 10.1016/j.jbc.2024.108084

Ryuji Yasutake, Hiroki Kuwajima, Ryuzaburo Yuki, Junna Tanaka, Youhei Saito, Yuji Nakayama

{"title":"Phosphorylation of Ephexin4 at Ser-41 contributes to chromosome alignment via RhoG activation in cell division.","authors":"Ryuji Yasutake, Hiroki Kuwajima, Ryuzaburo Yuki, Junna Tanaka, Youhei Saito, Yuji Nakayama","doi":"10.1016/j.jbc.2024.108084","DOIUrl":"https://doi.org/10.1016/j.jbc.2024.108084","url":null,"abstract":"Ephexin proteins are guanine nucleotide exchange factors for the Rho GTPases. We reported that Ephexin4 regulates M-phase progression downstream of phosphorylated EphA2, a receptor-type tyrosine kinase, through RhoG activation; however, the regulation of Ephexin4 during M phase remains unknown. In this study, a novel Ephexin4 phosphorylation site was identified at Ser41, exclusively in M phase. Ephexin4 knockdown prolonged the duration of M phase by activating the spindle assembly checkpoint, at which BubR1 was localized at the kinetochores of the misaligned chromosomes. This delay was alleviated by re-expression of wild-type, but not S41A Ephexin4. The Ephexin4 knockdown caused chromosome misalignment and reduced the RhoG localization to the plasma membrane. These phenotypes were rescued by re-expression of wild-type and phospho-mimic S41E mutant, but not the S41A mutant. Consistently, S41E mutant enhanced active RhoG levels, even in the interphase. Regardless of the Ephexin4 knockdown, active RhoG-G12V was localized at the plasma membrane. Furthermore, Ephexin4 knockdown exacerbated vincristine-induced chromosome misalignment, which was prevented by re-expressing the wild-type but not S41A Ephexin4. Overexpression of wild-type and S41E mutant, but not S41A mutant, resulted in an increased number of Madin-Darby canine kidney (MDCK) cysts with cells inside the lumen, indicating disruption of epithelial morphogenesis by deregulating Ephexin4/RhoG signaling in cell division. Our results suggest that Ephexin4 undergoes phosphorylation at Ser41 in cell division, and the phosphorylation is required for chromosome alignment through RhoG activation. Combined with mitosis-targeting agents, inhibition of Ephexin4 phosphorylation may represent a novel strategy for cancer chemotherapy.","PeriodicalId":15140,"journal":{"name":"Journal of Biological Chemistry","volume":" ","pages":"108084"},"PeriodicalIF":4.0,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142828928","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Reactivation and long-term stabilization of the [NiFe] Hox hydrogenase of Synechocystis sp. PCC6803 by glutathione after oxygen exposure. 暴露于氧气后谷胱甘肽对 Synechocystis sp.

IF 4 2区生物学

Journal of Biological Chemistry Pub Date : 2024-12-13 DOI: 10.1016/j.jbc.2024.108086

Merle Romig, Marie Eberwein, Darja Deobald, Andreas Schmid

{"title":"Reactivation and long-term stabilization of the [NiFe] Hox hydrogenase of Synechocystis sp. PCC6803 by glutathione after oxygen exposure.","authors":"Merle Romig, Marie Eberwein, Darja Deobald, Andreas Schmid","doi":"10.1016/j.jbc.2024.108086","DOIUrl":"https://doi.org/10.1016/j.jbc.2024.108086","url":null,"abstract":"Hydrogenases are key enzymes forming or consuming hydrogen. The inactivation of these transition metal biocatalysts with oxygen limits their biotechnological applications. Oxygen-sensitive hydrogenases are distinguished from oxygen-insensitive (tolerant) ones by their initial hydrogen turnover rates influenced by oxygen. Several hydrogenases, such as the oxygen-sensitive bidirectional [NiFe] Hox hydrogenase (Hox) of the unicellular cyanobacterium Synechocystis sp. PCC6803, are reactivated after oxygen-induced deactivation by redox mechanisms. In cyanobacteria, the glutathione (GSH) redox buffer majorly controls intracellular redox potentials. The relationship between Hox turnover rates and the redox potential in its natural reaction environment is not fully understood. We thus determined hydrogen oxidation rates as activities of Hox in cell-free extracts of Synechocystis using benzyl viologen as artificial electron acceptor. We found that GSH modulates Hox hydrogen oxidation rates under oxygen-free conditions. After oxygen exposure, it influences the maximal turnover rate and aids in the reactivation of Hox. Moreover, GSH stabilizes the long-term Hox activity under anoxic conditions and attenuates oxygen-induced deactivation of Hox in a concentration dependent manner, probably by fostering reactivation. Conversely, oxidized GSH (GSSG) negatively affects Hox activity and oxygen insensitivity. Using Blue Native PAGE followed by mass spectrometry, we showed that oxygen affects Hox complex integrity. The in-silico predicted structure of the Hox complex and complexome analyses reveal the formation of various Hox subcomplexes under different conditions. Our findings refine our current classification of oxygen-hydrogenase interactions beyond sensitive and insensitive, which is particularly important for understanding hydrogenase function under physiological conditions in future.","PeriodicalId":15140,"journal":{"name":"Journal of Biological Chemistry","volume":" ","pages":"108086"},"PeriodicalIF":4.0,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142828945","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

A Kinetic Model for Compound Heterozygous Pathogenic Variants in Tyrosyl-tRNA Synthetase Gene YARS2-Associated Neonatal Phenotype.

IF 4 2区生物学

Journal of Biological Chemistry Pub Date : 2024-12-13 DOI: 10.1016/j.jbc.2024.108092

Thomas Christian, Sunita Maharjan, Sitao Yin, Yuka Yamaki, Isao Masuda, Fenglin Li, Colleen Muraresku, Sheila Clever, Rebecca D Ganetzky, Ya-Ming Hou

{"title":"A Kinetic Model for Compound Heterozygous Pathogenic Variants in Tyrosyl-tRNA Synthetase Gene YARS2-Associated Neonatal Phenotype.","authors":"Thomas Christian, Sunita Maharjan, Sitao Yin, Yuka Yamaki, Isao Masuda, Fenglin Li, Colleen Muraresku, Sheila Clever, Rebecca D Ganetzky, Ya-Ming Hou","doi":"10.1016/j.jbc.2024.108092","DOIUrl":"https://doi.org/10.1016/j.jbc.2024.108092","url":null,"abstract":"Human genetic disorders are often caused by mutations of compound heterozygosity, where each allele of the mutant gene harbors a different genetic lesion. However, studies of such mutations are hampered, due to the lack of an appropriate model. Here we describe a kinetic model of compound heterozygous variants in an obligate enzyme dimer that contains one mutation in one monomer and the other mutation in the second monomer. This enzyme is encoded by human YARS2 for mitochondrial tyrosyl-tRNA synthetase (mt-TyrRS), which aminoacylates tyrosine to mt-tRNATyr. YARS2 is a member of the genes for mt-aminoacyl-tRNA synthetases, where pathogenic mutations present limited correlation between disease severity and enzyme activity. We identify a pair of compound heterozygous variants in YARS2 that is associated with neonatal fatality. We show that, while each mutation causes a minor-to-modest defect in aminoacylation in the homodimer of mt-TyrRS, the two mutations in trans synergistically reduce the enzyme activity to a greater effect. This kinetic model thus accurately recapitulates the disease severity, emphasizing its utility to study YARS2 mutations and its potential for generalization to other diseases with compound heterozygous mutations.","PeriodicalId":15140,"journal":{"name":"Journal of Biological Chemistry","volume":" ","pages":"108092"},"PeriodicalIF":4.0,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142828787","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Distinct autoregulatory roles of ELFN1 intracellular and extracellular domains on membrane trafficking, synaptic localization, and dimerization.

IF 4 2区生物学

Journal of Biological Chemistry Pub Date : 2024-12-13 DOI: 10.1016/j.jbc.2024.108073

Henry A Dunn, Simran K Dhaliwal, Chu-Ting Chang, Kirill A Martemyanov

{"title":"Distinct autoregulatory roles of ELFN1 intracellular and extracellular domains on membrane trafficking, synaptic localization, and dimerization.","authors":"Henry A Dunn, Simran K Dhaliwal, Chu-Ting Chang, Kirill A Martemyanov","doi":"10.1016/j.jbc.2024.108073","DOIUrl":"https://doi.org/10.1016/j.jbc.2024.108073","url":null,"abstract":"Synaptic adhesion molecules are essential components of the synapse, yet the diversity of these molecules and their associated functions remain to be fully characterized. Extracellular leucine rich repeat and fibronectin type III domain containing 1 (ELFN1) is a postsynaptic adhesion molecule in the brain that has been increasingly implicated in human neurological disease. ELFN1 is best known for trans-synaptically modulating group III metabotropic glutamate receptors (mGluRs). However, little is known about ELFN1 organization and regulation, which likely govern and precede its ultimate trans-synaptic engagement with group III mGluRs. Herein, we report that the intracellular ELFN1 domain controls membrane trafficking and post-synaptic localization of ELFN1. We pinpoint a ∼30 amino acid juxtamembranous region required for membrane-targeting and discover that ELFN1 exists as an obligate homodimer prior to its trafficking to the membrane. We determine that ELFN1 homodimerization is not appreciably affected by the intracellular region and instead utilizes the extracellular leucine rich repeats (LRR) domain. We find that a single membrane-targeting motif located in one protomer is sufficient for effective trafficking of the ELFN1 homodimer. We further demonstrate that the closest ELFN1 homolog, synaptic adhesion molecule ELFN2, exhibits similar properties and participates in heterodimerization with ELFN1. This establishes distinct autoregulatory roles of ELFN1 intracellular and extracellular domains on membrane trafficking, post-synaptic localization, and dimerization while indicating conservation of the mechanisms across the ELFN subfamily of cell adhesion molecules.","PeriodicalId":15140,"journal":{"name":"Journal of Biological Chemistry","volume":" ","pages":"108073"},"PeriodicalIF":4.0,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142828882","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Redirecting E3 Ubiquitin Ligases for Targeted Protein Degradation with Heterologous Recognition Domains. 利用异源识别域重定向 E3 泛素连接酶，实现有针对性的蛋白质降解。

IF 4 2区生物学

Journal of Biological Chemistry Pub Date : 2024-12-13 DOI: 10.1016/j.jbc.2024.108077

Huan Yang, Ge Zheng, Grace Y Li, Alia Alshaye, Stuart H Orkin

{"title":"Redirecting E3 Ubiquitin Ligases for Targeted Protein Degradation with Heterologous Recognition Domains.","authors":"Huan Yang, Ge Zheng, Grace Y Li, Alia Alshaye, Stuart H Orkin","doi":"10.1016/j.jbc.2024.108077","DOIUrl":"https://doi.org/10.1016/j.jbc.2024.108077","url":null,"abstract":"Targeted protein degradation (TPD) mediated by PROTACs (proteolysis targeting chimeras) or molecular glues is an emerging therapeutic strategy. Despite greater than 600 E3 ligases and their associated components, a limited number have been deployed in TPD. Those commonly used include cereblon (CRBN) and von Hippel-Lindau tumor suppressor (VHL), which are expressed widely and for which high affinity ligands are available. Limiting TPD to specific cells or tissues would be desirable in many settings. To this goal we have determined the potential of two erythroid cell-enriched E3 ligases, TRIM10 and TRIM58, to degrade a protein of interest, BCL11A, a validated therapeutic target for the β-hemoglobinopathies. We established a general strategy in which heterologous recognition domains replace the PRY-SPRY domain of TRIM10 and TRIM58. Recruitment of TRIM10 or TRIM58 to BCL11A by coiled-coil peptides, nanobodies, or the substrate recognition domain of CRBN led to its degradation. Our findings illustrate a strategy that may be widely useful in evaluating the TPD potential of other E3 ubiquitin ligases and provide a rationale for discovery of ligands for TRIM10 and TRIM58 for erythroid-selective depletion of proteins of interest.","PeriodicalId":15140,"journal":{"name":"Journal of Biological Chemistry","volume":" ","pages":"108077"},"PeriodicalIF":4.0,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142828950","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

The cobalamin processing enzyme of Trichoplax adhaerens. 白毛虫的钴胺素加工酶。

IF 4 2区生物学

Journal of Biological Chemistry Pub Date : 2024-12-13 DOI: 10.1016/j.jbc.2024.108089

Caroline Krams, Anna J Esser, Melissa Klenzendorf, Katharina Klotz, Ute Spiekerkoetter, Donald W Jacobsen, Clyde A Smith, Ailiena O Maggiolo, Luciana Hannibal

{"title":"The cobalamin processing enzyme of Trichoplax adhaerens.","authors":"Caroline Krams, Anna J Esser, Melissa Klenzendorf, Katharina Klotz, Ute Spiekerkoetter, Donald W Jacobsen, Clyde A Smith, Ailiena O Maggiolo, Luciana Hannibal","doi":"10.1016/j.jbc.2024.108089","DOIUrl":"https://doi.org/10.1016/j.jbc.2024.108089","url":null,"abstract":"Cobalamin (Cbl) is an essential cofactor for methionine synthase (MS) and methylmalonyl-CoA mutase (MUT), but it must first undergo chemical processing for utilization in animals. In humans, this processing comprises β-axial ligand cleavage and Cbl reduction and is performed by the enzyme MMACHC (HsCblC). Although the functionality of CblC is well-understood in higher order organisms, little is known about the evolutionary origin of these enzymes and the reactivity of CblCs in lower-order organisms with unique environmental and cellular conditions. Therefore, we investigated the CblC of Trichoplax adhaerens (TaCblC), a marine organism considered to be one of the earliest evolutionarily diverging and simplest living animals. The TaCblC sequence contained conserved residues important for Cbl processing in higher-order organisms. The predicted structure of TaCblC closely resembled known CblC structures and had features consistent with Cbl and co-substrate binding capabilities. Recombinantly expressed TaCblC could bind and process several Cbl analogues using glutathione or NADH as co-substrates, similarly to previously characterized CblCs, but with variable rates and dependencies on the presence of oxygen. Notably, TaCblC dealkylates methylcobalamin at a rate ca. 2-times higher than HsCblC, although this comes with a lower ratio of product to glutathione oxidation, suggesting higher unproductive electron transfer in the TaCblC system. This reflects differences in cellular conditions of the more ancient homologue, which lives in low oxygen levels and an environment of low Cbl biovailability (∼2 pM in sea water).","PeriodicalId":15140,"journal":{"name":"Journal of Biological Chemistry","volume":" ","pages":"108089"},"PeriodicalIF":4.0,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142828378","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Epitope mapping via in vitro deep mutational scanning methods and its applications. 通过体外深度突变扫描方法绘制表位图及其应用。

IF 4 2区生物学

Journal of Biological Chemistry Pub Date : 2024-12-12 DOI: 10.1016/j.jbc.2024.108072

Meredith M Keen, Alasdair D Keith, Eric A Ortlund

{"title":"Epitope mapping via in vitro deep mutational scanning methods and its applications.","authors":"Meredith M Keen, Alasdair D Keith, Eric A Ortlund","doi":"10.1016/j.jbc.2024.108072","DOIUrl":"https://doi.org/10.1016/j.jbc.2024.108072","url":null,"abstract":"Epitope mapping is a technique employed to define the region of an antigen that elicits an immune response, providing crucial insight into the structural architecture of the antigen as well as epitope-paratope interactions. With this breadth of knowledge, immunotherapies, diagnostics, and vaccines are being developed with a rational and data-supported design. Traditional epitope mapping methods are laborious, time-intensive, and often lack the ability to screen proteins in a high-throughput manner or provide high resolution. Deep mutational scanning (DMS), however, is revolutionizing the field as it can screen all possible single amino acid mutations and provide an efficient and high-throughput way to infer the structures of both linear and three-dimensional epitopes with high resolution. Currently, over fifty publications take this approach to efficiently identify enhancing or escaping mutations, with many then employing this information to rapidly develop broadly neutralizing antibodies, T-cell immunotherapies, vaccine platforms, or diagnostics. We provide a comprehensive review of the approaches to accomplish epitope mapping while also providing a summation of the development of DMS technology and its impactful applications.","PeriodicalId":15140,"journal":{"name":"Journal of Biological Chemistry","volume":" ","pages":"108072"},"PeriodicalIF":4.0,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142823829","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Diarylamidine activation of a brachiopod DEG/ENaC/ASIC channel.

IF 4 2区生物学

Journal of Biological Chemistry Pub Date : 2024-12-10 DOI: 10.1016/j.jbc.2024.108066

Josep Martí-Solans, Aina Børve, Andreas Hejnol, Timothy Lynagh

引用次数: 0

Spatial chromosome organization and adaptation of the radiation-resistant extremophile Deinococcus radiodurans. 抗辐射极端嗜热球菌（Deinococcus radiodurans）的空间染色体组织和适应性。

IF 4 2区生物学

Journal of Biological Chemistry Pub Date : 2024-12-10 DOI: 10.1016/j.jbc.2024.108068

Qin-Tian Qiu, Cai-Yun Zhang, Zhi-Peng Gao, Bin-Guang Ma

{"title":"Spatial chromosome organization and adaptation of the radiation-resistant extremophile Deinococcus radiodurans.","authors":"Qin-Tian Qiu, Cai-Yun Zhang, Zhi-Peng Gao, Bin-Guang Ma","doi":"10.1016/j.jbc.2024.108068","DOIUrl":"https://doi.org/10.1016/j.jbc.2024.108068","url":null,"abstract":"Radiation-resistant Deinococcus radiodurans is an extremophilic microorganism capable of withstanding high levels of ionizing radiation and chemical mutagens. It possesses remarkable DNA repair capability and serves as a model organism for studying stress resistance mechanism. However, our understanding on the spatial chromosome organization of this species remains limited. In this study, we employed chromosome conformation capture (3C) technology to determine the 3D genome structure of D. radiodurans and to further investigate the changes of chromosome conformation induced by ultraviolet (UV) irradiation. We observed that UV irradiation reduced short-range chromosome interactions, and smaller chromosomal interaction domains (CIDs) merged to form larger CIDs. Integrating transcriptomic data analysis, we found that the majority of upregulated differentially expressed genes were significantly enriched near specific CID boundaries. Specially, we comprehensively elucidated that the nucleoid-associated protein DrEbfC as a global regulatory factor for gene expression, may modulate the efficiency of relevant metabolic pathways by altering the local chromosome structure, thereby influencing the physiological state of the bacterium. Overall, our study revealed the chromosome conformations of D. radiodurans under different conditions, and offered valuable insights into the molecular response mechanism of this extremophile to survival stresses.","PeriodicalId":15140,"journal":{"name":"Journal of Biological Chemistry","volume":" ","pages":"108068"},"PeriodicalIF":4.0,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142818039","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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