The Journal of Biological Chemistry最新文献

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Insulin-like growth factor binding protein-3 mediates hyperosmolar stress-induced mitophagy through the mechanistic target of rapamycin. 胰岛素样生长因子结合蛋白-3通过雷帕霉素的机制靶点介导高渗应激诱导的线粒体自噬。
The Journal of Biological Chemistry Pub Date : 2023-11-01 Epub Date: 2023-09-09 DOI: 10.1016/j.jbc.2023.105239
Whitney Stuard Sambhariya, Ian J Trautmann, Danielle M Robertson
{"title":"Insulin-like growth factor binding protein-3 mediates hyperosmolar stress-induced mitophagy through the mechanistic target of rapamycin.","authors":"Whitney Stuard Sambhariya, Ian J Trautmann, Danielle M Robertson","doi":"10.1016/j.jbc.2023.105239","DOIUrl":"10.1016/j.jbc.2023.105239","url":null,"abstract":"<p><p>Hyperosmolarity of the ocular surface triggers inflammation and pathological damage in dry eye disease (DED). In addition to a reduction in quality of life, DED causes vision loss and when severe, blindness. Mitochondrial dysfunction occurs as a consequence of hyperosmolar stress. We have previously reported on a role for the insulin-like growth factor binding protein-3 (IGFBP-3) in the regulation of mitochondrial ultrastructure and metabolism in mucosal surface epithelial cells; however, this appears to be context-specific. Due to the finding that IGFBP-3 expression is decreased in response to hyperosmolar stress in vitro and in an animal model of DED, we next sought to determine whether the hyperosmolar stress-mediated decrease in IGFBP-3 alters mitophagy, a key mitochondrial quality control mechanism. Here we show that hyperosmolar stress induces mitophagy through differential regulation of BNIP3L/NIX and PINK1-mediated pathways. In corneal epithelial cells, this was independent of p62. The addition of exogenous IGFBP-3 abrogated the increase in mitophagy. This occurred through regulation of mTOR, highlighting the existence of a new IGFBP-3-mTOR signaling pathway. Together, these findings support a novel role for IGFBP-3 in mediating mitochondrial quality control in DED and have broad implications for epithelial tissues subject to hyperosmolar stress and other mitochondrial diseases.</p>","PeriodicalId":22621,"journal":{"name":"The Journal of Biological Chemistry","volume":" ","pages":"105239"},"PeriodicalIF":0.0,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10637961/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10202581","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Phase plane dynamics of ERK phosphorylation. ERK磷酸化的相平面动力学。
The Journal of Biological Chemistry Pub Date : 2023-11-01 Epub Date: 2023-09-09 DOI: 10.1016/j.jbc.2023.105234
Stanislav Y Shvartsman, Sarah McFann, Martin Wühr, Boris Y Rubinstein
{"title":"Phase plane dynamics of ERK phosphorylation.","authors":"Stanislav Y Shvartsman, Sarah McFann, Martin Wühr, Boris Y Rubinstein","doi":"10.1016/j.jbc.2023.105234","DOIUrl":"10.1016/j.jbc.2023.105234","url":null,"abstract":"<p><p>The extracellular signal-regulated kinase (ERK) controls multiple critical processes in the cell and is deregulated in human cancers, congenital abnormalities, immune diseases, and neurodevelopmental syndromes. Catalytic activity of ERK requires dual phosphorylation by an upstream kinase, in a mechanism that can be described by two sequential Michaelis-Menten steps. The estimation of individual reaction rate constants from kinetic data in the full mechanism has proved challenging. Here, we present an analytically tractable approach to parameter estimation that is based on the phase plane representation of ERK activation and yields two combinations of six reaction rate constants in the detailed mechanism. These combinations correspond to the ratio of the specificities of two consecutive phosphorylations and the probability that monophosphorylated substrate does not dissociate from the enzyme before the second phosphorylation. The presented approach offers a language for comparing the effects of mutations that disrupt ERK activation and function in vivo. As an illustration, we use phase plane representation to analyze dual phosphorylation under heterozygous conditions, when two enzyme variants compete for the same substrate.</p>","PeriodicalId":22621,"journal":{"name":"The Journal of Biological Chemistry","volume":" ","pages":"105234"},"PeriodicalIF":0.0,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10616409/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10202584","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Anti-tau antibodies targeting a conformation-dependent epitope selectively bind seeds. 靶向构象依赖性表位的抗τ抗体选择性结合种子。
The Journal of Biological Chemistry Pub Date : 2023-11-01 Epub Date: 2023-09-14 DOI: 10.1016/j.jbc.2023.105252
Brian D Hitt, Ankit Gupta, Ruhar Singh, Ting Yang, Joshua D Beaver, Ping Shang, Charles L White, Lukasz A Joachimiak, Marc I Diamond
{"title":"Anti-tau antibodies targeting a conformation-dependent epitope selectively bind seeds.","authors":"Brian D Hitt, Ankit Gupta, Ruhar Singh, Ting Yang, Joshua D Beaver, Ping Shang, Charles L White, Lukasz A Joachimiak, Marc I Diamond","doi":"10.1016/j.jbc.2023.105252","DOIUrl":"10.1016/j.jbc.2023.105252","url":null,"abstract":"<p><p>Neurodegenerative tauopathies are caused by the transition of tau protein from a monomer to a toxic aggregate. They include Alzheimer disease (AD), progressive supranuclear palsy (PSP), corticobasal degeneration (CBD), and Pick disease (PiD). We have previously proposed that tau monomer exists in two conformational ensembles: an inert form (M<sub>i</sub>), which does not self-assemble, and seed-competent form (M<sub>s</sub>), which self-assembles and templates ordered assembly growth. We proposed that cis/trans isomerization of tau at P301, the site of dominant disease-associated S/L missense mutations, might underlie the transition of wild-type tau to a seed-competent state. Consequently, we created monoclonal antibodies using non-natural antigens consisting of fluorinated proline (P∗) at the analogous P270 in repeat 1 (R1), biased toward the trans-configuration at either the R1/R2 (TENLKHQP∗GGGKVQIINKK) or the R1/R3 (TENLKHQP∗GGGKVQIVYK) interfaces. Two antibodies, MD2.2 and MD3.1, efficiently immunoprecipitated soluble seeds from AD and PSP but not CBD or PiD brain samples. The antibodies efficiently stained brain samples of AD, PSP, and PiD, but not CBD. They did not immunoprecipitate or immunostain tau from the control brain. Creation of potent anti-seed antibodies based on the trans-proline epitope implicates local unfolding around P301 in pathogenesis. MD2.2 and MD3.1 may also be useful for therapy and diagnosis.</p>","PeriodicalId":22621,"journal":{"name":"The Journal of Biological Chemistry","volume":" ","pages":"105252"},"PeriodicalIF":0.0,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10582770/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10316834","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The kinesin-14 family motor protein KIFC2 promotes prostate cancer progression by regulating p65. 驱动蛋白-14家族运动蛋白KIFC2通过调节p65促进前列腺癌症进展。
The Journal of Biological Chemistry Pub Date : 2023-11-01 Epub Date: 2023-09-14 DOI: 10.1016/j.jbc.2023.105253
Xinyu Liu, Yu Lin, Weibing Long, Renzheng Yi, Xiongfeng Zhang, Chaoqun Xie, Na Jin, Ziran Qiu, Xiaobing Liu
{"title":"The kinesin-14 family motor protein KIFC2 promotes prostate cancer progression by regulating p65.","authors":"Xinyu Liu, Yu Lin, Weibing Long, Renzheng Yi, Xiongfeng Zhang, Chaoqun Xie, Na Jin, Ziran Qiu, Xiaobing Liu","doi":"10.1016/j.jbc.2023.105253","DOIUrl":"10.1016/j.jbc.2023.105253","url":null,"abstract":"<p><p>The kinesin-14 motor proteins play important roles in tumor development and drug resistance and have been reported as potential biomarkers or therapeutic targets for tumor treatment. However, kinesin family member C2 (KIFC2), one of the kinesin-14 motor family members, remains largely unknown in prostate cancer (PCa) progression. Here, we used the GEO and The Cancer Genome Atlas datasets, Western blotting, and immunohistochemistry analyses to detect KIFC2 expression in PCa tissues. Additionally, a series of in vivo and in vitro experiments were utilized to demonstrate the roles of KIFC2 in PCa cells. We found that KIFC2 was highly expressed and positively correlated with the clinicopathological characteristics in PCa. Functional experiments indicated that KIFC2 could promote PCa progression. Furthermore, we performed an analysis of the KEGG and GSEA databases, subcellular fractionation, and immunofluorescence to investigate the potential mechanisms of KIFC2 in PCa. We confirmed that KIFC2 could regulate the NF-κB pathway via mediating NF-κB p65 protein expression and nuclear translocation thereby promoting PCa progression and chemotherapeutic resistance. Together, our results suggest that KIFC2 is overexpressed in PCa. By regulating the NF-κB pathway, KIFC2 may play a crucial role in PCa.</p>","PeriodicalId":22621,"journal":{"name":"The Journal of Biological Chemistry","volume":" ","pages":"105253"},"PeriodicalIF":0.0,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10590982/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10269211","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
An essential signaling function of cytoplasmic NELFB is independent of RNA polymerase II pausing. 细胞质NELFB的一种基本信号传导功能与RNA聚合酶II暂停无关。
The Journal of Biological Chemistry Pub Date : 2023-11-01 Epub Date: 2023-09-17 DOI: 10.1016/j.jbc.2023.105259
Haihui Pan, Xiaolong Cheng, Pedro Felipe Gardeazábal Rodríguez, Xiaowen Zhang, Inhee Chung, Victor X Jin, Wei Li, Yanfen Hu, Rong Li
{"title":"An essential signaling function of cytoplasmic NELFB is independent of RNA polymerase II pausing.","authors":"Haihui Pan, Xiaolong Cheng, Pedro Felipe Gardeazábal Rodríguez, Xiaowen Zhang, Inhee Chung, Victor X Jin, Wei Li, Yanfen Hu, Rong Li","doi":"10.1016/j.jbc.2023.105259","DOIUrl":"10.1016/j.jbc.2023.105259","url":null,"abstract":"<p><p>The four-subunit negative elongation factor (NELF) complex mediates RNA polymerase II (Pol II) pausing at promoter-proximal regions. Ablation of individual NELF subunits destabilizes the NELF complex and causes cell lethality, leading to the prevailing concept that NELF-mediated Pol II pausing is essential for cell proliferation. Using separation-of-function mutations, we show here that NELFB function in cell proliferation can be uncoupled from that in Pol II pausing. NELFB mutants sequestered in the cytoplasm and deprived of NELF nuclear function still support cell proliferation and part of the NELFB-dependent transcriptome. Mechanistically, cytoplasmic NELFB physically and functionally interacts with prosurvival signaling kinases, most notably phosphatidylinositol-3-kinase/AKT. Ectopic expression of membrane-tethered phosphatidylinositol-3-kinase/AKT partially bypasses the role of NELFB in cell proliferation, but not Pol II occupancy. Together, these data expand the current understanding of the physiological impact of Pol II pausing and underscore the multiplicity of the biological functions of individual NELF subunits.</p>","PeriodicalId":22621,"journal":{"name":"The Journal of Biological Chemistry","volume":" ","pages":"105259"},"PeriodicalIF":0.0,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10591015/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10634086","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Co-folding and RNA activation of poliovirus 3Cpro polyprotein precursors. 脊髓灰质炎病毒3Cpro多蛋白前体的共折叠和RNA激活。
The Journal of Biological Chemistry Pub Date : 2023-11-01 Epub Date: 2023-09-15 DOI: 10.1016/j.jbc.2023.105258
Grace Campagnola, Olve Peersen
{"title":"Co-folding and RNA activation of poliovirus 3C<sup>pro</sup> polyprotein precursors.","authors":"Grace Campagnola, Olve Peersen","doi":"10.1016/j.jbc.2023.105258","DOIUrl":"10.1016/j.jbc.2023.105258","url":null,"abstract":"<p><p>Positive-strand RNA viruses use long open reading frames to express large polyproteins that are processed into individual proteins by viral proteases. Polyprotein processing is highly regulated and yields intermediate species with different functions than the fully processed proteins, increasing the biochemical diversity of the compact viral genome while also presenting challenges in that proteins must remain stably folded in multiple contexts. We have used circular dichroism spectroscopy and single molecule microscopy to examine the solution structure and self-association of the poliovirus P3 region protein composed of membrane binding 3A, RNA priming 3B (VPg), 3C<sup>pro</sup> protease, and 3D<sup>pol</sup> RNA-dependent RNA polymerase proteins. Our data indicate that co-folding interactions within the 3ABC segment stabilize the conformational state of the 3C protease region, and this stabilization requires the full-length 3A and 3B proteins. Enzymatic activity assays show that 3ABC is also an active protease, and it cleaves peptide substrates at rates comparable to 3C<sup>pro</sup>. The cleavage of a larger polyprotein substrate is stimulated by the addition of RNA, and 3ABC<sup>pro</sup> becomes 20-fold more active than 3C<sup>pro</sup> in the presence of stoichiometric amounts of viral cre RNA. The data suggest that co-folding within the 3ABC region results in a protease that can be highly activated toward certain cleavage sites by localization to specific RNA elements within the viral replication center, providing a mechanism for regulating viral polyprotein processing.</p>","PeriodicalId":22621,"journal":{"name":"The Journal of Biological Chemistry","volume":" ","pages":"105258"},"PeriodicalIF":0.0,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10590986/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10338566","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Proteomic mapping reveals dysregulated angiogenesis in the cerebral arteries of rats with early-onset hypertension. 蛋白质组学图谱显示早发性高血压大鼠脑动脉血管生成失调。
The Journal of Biological Chemistry Pub Date : 2023-10-01 Epub Date: 2023-09-01 DOI: 10.1016/j.jbc.2023.105221
Joakim A Bastrup, Thomas A Jepps
{"title":"Proteomic mapping reveals dysregulated angiogenesis in the cerebral arteries of rats with early-onset hypertension.","authors":"Joakim A Bastrup,&nbsp;Thomas A Jepps","doi":"10.1016/j.jbc.2023.105221","DOIUrl":"10.1016/j.jbc.2023.105221","url":null,"abstract":"<p><p>Hypertension is associated with the presence of vascular abnormalities, including remodeling and rarefaction. These processes play an important role in cerebrovascular disease development; however, the mechanistic changes leading to these diseases are not well characterized. Using data-independent acquisition-based mass spectrometry analysis, here we determined the protein changes in cerebral arteries in pre- and early-onset hypertension from the spontaneously hypertensive rat (SHR), a model that resembles essential hypertension in humans. Our analysis identified 125 proteins with expression levels that were significantly upregulated or downregulated in 12-week-old spontaneously hypertensive rats compared to normotensive Wistar Kyoto rats. Using an angiogenesis enrichment analysis, we further identified a critical imbalance in angiogenic proteins that promoted an anti-angiogenic profile in cerebral arteries at early onset of hypertension. In a comparison to previously published data, we demonstrate that this angiogenic imbalance is not present in mesenteric and renal arteries from age-matched SHRs. Finally, we identified two proteins (Fbln5 and Cdh13), whose expression levels were critically altered in cerebral arteries compared to the other arterial beds. The observation of an angiogenic imbalance in cerebral arteries from the SHR reveals critical protein changes in the cerebrovasculature at the early onset of hypertension and provides novel insights into the early pathology of cerebrovascular disease.</p>","PeriodicalId":22621,"journal":{"name":"The Journal of Biological Chemistry","volume":" ","pages":"105221"},"PeriodicalIF":0.0,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10558802/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10202060","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Characterization of a new family of 6-sulfo-N-acetylglucosaminidases. 一个新的6-磺基-N-乙酰基葡糖苷酶家族的鉴定。
The Journal of Biological Chemistry Pub Date : 2023-10-01 Epub Date: 2023-09-01 DOI: 10.1016/j.jbc.2023.105214
Rajneesh K Bains, Seyed A Nasseri, Feng Liu, Jacob F Wardman, Peter Rahfeld, Stephen G Withers
{"title":"Characterization of a new family of 6-sulfo-N-acetylglucosaminidases.","authors":"Rajneesh K Bains,&nbsp;Seyed A Nasseri,&nbsp;Feng Liu,&nbsp;Jacob F Wardman,&nbsp;Peter Rahfeld,&nbsp;Stephen G Withers","doi":"10.1016/j.jbc.2023.105214","DOIUrl":"10.1016/j.jbc.2023.105214","url":null,"abstract":"<p><p>Sulfation is widespread in nature and plays an important role in modulating biological function. Among the strategies developed by microbes to access sulfated oligosaccharides as a nutrient source is the production of 6-sulfoGlcNAcases to selectively release 6-sulfoGlcNAc from target oligosaccharides. Thus far, all 6-sulfoGlcNAcases identified have belonged to the large GH20 family of β-hexosaminidases. Ηere, we identify and characterize a new, highly specific non-GH20 6-sulfoGlcNAcase from Streptococcus pneumoniae TIGR4, Sp_0475 with a greater than 110,000-fold preference toward N-acetyl-β-D-glucosamine-6-sulfate substrates over the nonsulfated version. Sp_0475 shares distant sequence homology with enzymes of GH20 and with the newly formed GH163 family. However, the sequence similarity between them is sufficiently low that Sp_0475 has been assigned as the founding member of a new glycoside hydrolase family, GH185. By combining results from site-directed mutagenesis with mechanistic studies and bioinformatics we provide insight into the substrate specificity, mechanism, and key active site residues of Sp_0475. Enzymes of the GH185 family follow a substrate-assisted mechanism, consistent with their distant homology to the GH20 family, but the catalytic residues involved are quite different. Taken together, our results highlight in more detail how microbes can degrade sulfated oligosaccharides for nutrients.</p>","PeriodicalId":22621,"journal":{"name":"The Journal of Biological Chemistry","volume":" ","pages":"105214"},"PeriodicalIF":0.0,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/9b/d9/main.PMC10570127.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10202061","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Molecular regulatory mechanism of human myosin-7a. 人肌球蛋白7a的分子调控机制。
The Journal of Biological Chemistry Pub Date : 2023-10-01 Epub Date: 2023-09-09 DOI: 10.1016/j.jbc.2023.105243
Alexandra Holló, Neil Billington, Yasuharu Takagi, András Kengyel, James R Sellers, Rong Liu
{"title":"Molecular regulatory mechanism of human myosin-7a.","authors":"Alexandra Holló, Neil Billington, Yasuharu Takagi, András Kengyel, James R Sellers, Rong Liu","doi":"10.1016/j.jbc.2023.105243","DOIUrl":"10.1016/j.jbc.2023.105243","url":null,"abstract":"<p><p>Myosin-7a is an actin-based motor protein essential for vision and hearing. Mutations of myosin-7a cause type 1 Usher syndrome, the most common and severe form of deafblindness in humans. The molecular mechanisms that govern its mechanochemistry remain poorly understood, primarily because of the difficulty of purifying stable intact protein. Here, we recombinantly produce the complete human myosin-7a holoenzyme in insect cells and characterize its biochemical and motile properties. Unlike the Drosophila ortholog that primarily associates with calmodulin (CaM), we found that human myosin-7a utilizes a unique combination of light chains including regulatory light chain, CaM, and CaM-like protein 4. Our results further reveal that CaM-like protein 4 does not function as a Ca<sup>2+</sup> sensor but plays a crucial role in maintaining the lever arm's structural-functional integrity. Using our recombinant protein system, we purified two myosin-7a splicing isoforms that have been shown to be differentially expressed along the cochlear tonotopic axis. We show that they possess distinct mechanoenzymatic properties despite differing by only 11 amino acids at their N termini. Using single-molecule in vitro motility assays, we demonstrate that human myosin-7a exists as an autoinhibited monomer and can move processively along actin when artificially dimerized or bound to cargo adaptor proteins. These results suggest that myosin-7a can serve multiple roles in sensory systems such as acting as a transporter or an anchor/force sensor. Furthermore, our research highlights that human myosin-7a has evolved unique regulatory elements that enable precise tuning of its mechanical properties suitable for mammalian auditory functions.</p>","PeriodicalId":22621,"journal":{"name":"The Journal of Biological Chemistry","volume":" ","pages":"105243"},"PeriodicalIF":0.0,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/94/ac/main.PMC10579538.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10202586","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Translation factor and RNA binding protein mRNA interactomes support broader RNA regulons for posttranscriptional control. 翻译因子和RNA结合蛋白mRNA相互作用体支持更广泛的RNA调节子进行转录后控制。
The Journal of Biological Chemistry Pub Date : 2023-10-01 Epub Date: 2023-08-24 DOI: 10.1016/j.jbc.2023.105195
Christopher J Kershaw, Michael G Nelson, Lydia M Castelli, Martin D Jennings, Jennifer Lui, David Talavera, Chris M Grant, Graham D Pavitt, Simon J Hubbard, Mark P Ashe
{"title":"Translation factor and RNA binding protein mRNA interactomes support broader RNA regulons for posttranscriptional control.","authors":"Christopher J Kershaw,&nbsp;Michael G Nelson,&nbsp;Lydia M Castelli,&nbsp;Martin D Jennings,&nbsp;Jennifer Lui,&nbsp;David Talavera,&nbsp;Chris M Grant,&nbsp;Graham D Pavitt,&nbsp;Simon J Hubbard,&nbsp;Mark P Ashe","doi":"10.1016/j.jbc.2023.105195","DOIUrl":"10.1016/j.jbc.2023.105195","url":null,"abstract":"<p><p>The regulation of translation provides a rapid and direct mechanism to modulate the cellular proteome. In eukaryotes, an established model for the recruitment of ribosomes to mRNA depends upon a set of conserved translation initiation factors. Nevertheless, how cells orchestrate and define the selection of individual mRNAs for translation, as opposed to other potential cytosolic fates, is poorly understood. We have previously found significant variation in the interaction between individual mRNAs and an array of translation initiation factors. Indeed, mRNAs can be separated into different classes based upon these interactions to provide a framework for understanding different modes of translation initiation. Here, we extend this approach to include new mRNA interaction profiles for additional proteins involved in shaping the cytoplasmic fate of mRNAs. This work defines a set of seven mRNA clusters, based on their interaction profiles with 12 factors involved in translation and/or RNA binding. The mRNA clusters share both physical and functional characteristics to provide a rationale for the interaction profiles. Moreover, a comparison with mRNA interaction profiles from a host of RNA binding proteins suggests that there are defined patterns in the interactions of functionally related mRNAs. Therefore, this work defines global cytoplasmic mRNA binding modules that likely coordinate the synthesis of functionally related proteins.</p>","PeriodicalId":22621,"journal":{"name":"The Journal of Biological Chemistry","volume":" ","pages":"105195"},"PeriodicalIF":0.0,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10562868/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10145230","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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