The Protein Journal最新文献_第9页

Use of 2D FFT and DTW in Protein Sequence Comparison 2D FFT和DTW在蛋白质序列比较中的应用。

IF 1.9 4区生物学

The Protein Journal Pub Date : 2023-10-17 DOI: 10.1007/s10930-023-10160-2

Jayanta Pal, Soumen Ghosh, Bansibadan Maji, Dilip Kumar Bhattacharya

{"title":"Use of 2D FFT and DTW in Protein Sequence Comparison","authors":"Jayanta Pal, Soumen Ghosh, Bansibadan Maji, Dilip Kumar Bhattacharya","doi":"10.1007/s10930-023-10160-2","DOIUrl":"10.1007/s10930-023-10160-2","url":null,"abstract":"<div><p>Protein sequence comparison remains a challenging work for the researchers owing to the computational complexity due to the presence of 20 amino acids compared with only four nucleotides in Genome sequences. Further, protein sequences of different species are of different lengths; it throws additional changes to the researchers to develop methods, specially alignment-free methods, to compare protein sequences. In this work, an efficient technique to compare protein sequences is developed by a graphical representation. First, the classified grouping of 20 amino acids with a cardinality of 4 based on polar class is considered to narrow down the representational range from 20 to 4. Then a unit vector technique based on a two-quadrant Cartesian system is proposed to provide a new two-dimensional graphical representation of the protein sequence. Now, two approaches are proposed to cope with the varying lengths of protein sequences from various species: one uses Dynamic Time Warping (DTW), while the other one uses a two-dimensional Fast Fourier Transform (2D FFT). Next, the effectiveness of these two techniques is analyzed using two evaluation criteria—quantitative measures based on symmetric distance (SD) and computational speed. An analysis is performed on five data sets of 9 ND4, 9 ND5, 9 ND6, 12 Baculovirus, and 24 TF proteins under the two methods. It is found that the FFT-based method produces the same results as DTW but in less computational time. It is found that the result of the proposed method agrees with the known biological reference. Further, the present method produces better clustering than the existing ones.</p></div>","PeriodicalId":793,"journal":{"name":"The Protein Journal","volume":"43 1","pages":"1 - 11"},"PeriodicalIF":1.9,"publicationDate":"2023-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41242862","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Improvement of α-amino Ester Hydrolase Stability via Computational Protein Design 通过计算蛋白质设计提高α-氨基酯水解酶的稳定性。

IF 3 4区生物学

The Protein Journal Pub Date : 2023-10-11 DOI: 10.1007/s10930-023-10155-z

Colton E. Lagerman, Emily A. Joe, Martha A. Grover, Ronald W. Rousseau, Andreas S. Bommarius

引用次数: 0

Amine Group Surface-Functionalized Carbon Quantum Dots Exhibit Anti-amyloidogenic Effects Towards Hen Egg White Lysozyme by Inducing Formation of Nontoxic Spherical Aggregates 胺基表面功能化碳量子点通过诱导无毒球形聚集体的形成对母鸡蛋清溶菌酶表现出抗淀粉样蛋白生成作用。

IF 3 4区生物学

The Protein Journal Pub Date : 2023-10-07 DOI: 10.1007/s10930-023-10157-x

M. P. Taraka Prabhu, Shreya Chrungoo, Nandini Sarkar

{"title":"Amine Group Surface-Functionalized Carbon Quantum Dots Exhibit Anti-amyloidogenic Effects Towards Hen Egg White Lysozyme by Inducing Formation of Nontoxic Spherical Aggregates","authors":"M. P. Taraka Prabhu, Shreya Chrungoo, Nandini Sarkar","doi":"10.1007/s10930-023-10157-x","DOIUrl":"10.1007/s10930-023-10157-x","url":null,"abstract":"<div><p>The tendency of polypeptide chains to deviate from their conventional protein folding pathway and instead get trapped as off-pathway intermediates, has been a matter of great concern. These off-pathway intermediates eventually lead to the formation of insoluble, ordered fibrillar aggregates called amyloids, which are responsible for a host of neurodegenerative diseases like Alzheimer’s disease, Parkinson’s disease and Type II diabetes. In spite of extensive research, development of an effective therapeutic strategy against amyloidosis still remains elusive. In recent times, carbon quantum dots (CQD) have grabbed the attention of researchers against amyloidogenesis due to their ease of preparation, aqueous soluble nature, unique optical properties, high surface to volume ratio, physio-chemical properties, semi-conducting nature and mainly biocompatible. In the current study, we have reported an easy-to-prepare procedure for synthesis of amine group surface functionalized CQDs from commonly available kitchen spices with anti-oxidant properties. The as-synthesized CQDs were evaluated for their anti-amyloidogenic properties towards Hen Egg White Lysozyme (HEWL). Our results clearly show that the surfaced functionalized CQDs were able to interact with HEWL, thereby forming a stable complex, which was resistant towards amyloid formation and instead lead to the formation of non-toxic globular aggregates.</p></div>","PeriodicalId":793,"journal":{"name":"The Protein Journal","volume":"42 6","pages":"728 - 740"},"PeriodicalIF":3.0,"publicationDate":"2023-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41150193","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Kennedy Epitope (KE)-dependent Retrograde Transport of Efficiently Cleaved HIV-1 Envelopes (Envs) and its Effect on Env Cell Surface Expression and Viral Particle Formation 有效切割的HIV-1包膜（Envs）的肯尼迪表位（KE）依赖性逆转录转运及其对Env细胞表面表达和病毒颗粒形成的影响。

IF 1.9 4区生物学

The Protein Journal Pub Date : 2023-10-04 DOI: 10.1007/s10930-023-10161-1

Supratik Das, Hilal Ahmad Parray, Adarsh Kumar Chiranjivi, Prince Kumar, Abhishek Goswami, Manish Bansal, Deepak Kumar Rathore, Rajesh Kumar, Sweety Samal

{"title":"Kennedy Epitope (KE)-dependent Retrograde Transport of Efficiently Cleaved HIV-1 Envelopes (Envs) and its Effect on Env Cell Surface Expression and Viral Particle Formation","authors":"Supratik Das, Hilal Ahmad Parray, Adarsh Kumar Chiranjivi, Prince Kumar, Abhishek Goswami, Manish Bansal, Deepak Kumar Rathore, Rajesh Kumar, Sweety Samal","doi":"10.1007/s10930-023-10161-1","DOIUrl":"10.1007/s10930-023-10161-1","url":null,"abstract":"<div><p>Efficiently cleaved HIV-1 Envs are the closest mimics of functional Envs as they specifically expose only bNAb (broadly neutralizing antibody) epitopes and not non-neutralizing ones, making them suitable for developing vaccine immunogens. We have previously identified several efficiently cleaved Envs from clades A, B, C and B/C. We also described that truncation of the CT (C-terminal tail) of a subset of these Envs, but not others, impairs their ectodomain conformation/antigenicity on the cell surface in a CT conserved hydrophilic domain (CHD) or Kennedy epitope (KE)-dependent manner. Here, we report that those Envs (4 − 2.J41 and JRCSF), whose native-like ectodomain conformation/antigenicity on the cell surface is disrupted upon CT truncation, but not other Envs like JRFL, whose CT truncation does not have an effect on ectodomain integrity on the cell surface, are also defective in retrograde transport from early to late endosomes. Restoration of the CHD/KE in the CT of these Envs restores wild-type levels of distribution between early and late endosomes. In the presence of retrograde transport inhibitor Retro 2, cell surface expression of 4 − 2.J41 and JRCSF Envs increases [as does in the presence of Rab7a DN and Rab7b DN (DN: dominant negative)] but particle formation decreases for 4 − 2.J41 and JRCSF Env pseudotyped viruses. Our results show for the first time a correlation between CT-dependent, CHD/KE regulated retrograde transport and cell surface expression/viral particle formation of these efficiently cleaved Envs. Based on our results we hypothesize that a subset of these efficiently cleaved Envs use a CT-dependent, CHD/KE-mediated mechanism for assembly and release from late endosomes.</p></div>","PeriodicalId":793,"journal":{"name":"The Protein Journal","volume":"43 2","pages":"375 - 386"},"PeriodicalIF":1.9,"publicationDate":"2023-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41170262","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Purification and Biochemical Characterization of the DNA Binding Domain of the Nitrogenase Transcriptional Activator NifA from Gluconacetobacter diazotrophicus 重氮葡萄球菌固氮酶转录激活剂NifA DNA结合域的纯化及生化性质研究。

IF 3 4区生物学

The Protein Journal Pub Date : 2023-10-03 DOI: 10.1007/s10930-023-10158-w

Heidi G. Standke, Lois Kim, Cedric P. Owens

{"title":"Purification and Biochemical Characterization of the DNA Binding Domain of the Nitrogenase Transcriptional Activator NifA from Gluconacetobacter diazotrophicus","authors":"Heidi G. Standke, Lois Kim, Cedric P. Owens","doi":"10.1007/s10930-023-10158-w","DOIUrl":"10.1007/s10930-023-10158-w","url":null,"abstract":"<div><p>NifA is a σ<sup>54</sup> activator that turns on bacterial nitrogen fixation under reducing conditions and when fixed cellular nitrogen levels are low. The redox sensing mechanism in NifA is poorly understood. In α- and β-proteobacteria, redox sensing involves two pairs of Cys residues within and immediately following the protein’s central AAA<sup>+</sup> domain. In this work, we examine if an additional Cys pair that is part of a C(X)<sub>5</sub> C motif and located immediately upstream of the DNA binding domain of NifA from the α-proteobacterium <i>Gluconacetobacter diazotrophicus</i> (<i>Gd</i>) is involved in redox sensing. We hypothesize that the Cys residues’ redox state may directly influence the DNA binding domain’s DNA binding affinity and/or alter the protein’s oligomeric sate. Two DNA binding domain constructs were generated, a longer construct (2C-DBD), consisting of the DNA binding domain with the upstream Cys pair, and a shorter construct (NC-DBD) that lacks the Cys pair. The <i>K</i><sub>d</sub> of NC-DBD for its cognate DNA sequence (nifH-UAS) is equal to 20.0 µM. The <i>K</i><sub>d</sub> of 2C-DBD for nifH-UAS when the Cys pair is oxidized is 34.5 µM. Reduction of the disulfide bond does not change the DNA binding affinity. Additional experiments indicate that the redox state of the Cys residues does not influence the secondary structure or oligomerization state of the NifA DNA binding domain. Together, these results demonstrate that the Cys pair upstream of the DNA binding domain of <i>Gd</i>-NifA does not regulate DNA binding or domain dimerization in a redox dependent manner.</p></div>","PeriodicalId":793,"journal":{"name":"The Protein Journal","volume":"42 6","pages":"802 - 810"},"PeriodicalIF":3.0,"publicationDate":"2023-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s10930-023-10158-w.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41169297","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Protein Kinases and their Inhibitors Implications in Modulating Disease Progression 蛋白激酶及其抑制剂在调节疾病进展中的意义。

IF 3 4区生物学

The Protein Journal Pub Date : 2023-09-28 DOI: 10.1007/s10930-023-10159-9

Rabiya Ahsan, Mohd Muazzam Khan, Anuradha Mishra, Gazala Noor, Usama Ahmad

{"title":"Protein Kinases and their Inhibitors Implications in Modulating Disease Progression","authors":"Rabiya Ahsan, Mohd Muazzam Khan, Anuradha Mishra, Gazala Noor, Usama Ahmad","doi":"10.1007/s10930-023-10159-9","DOIUrl":"10.1007/s10930-023-10159-9","url":null,"abstract":"<div><p>Protein phosphorylation plays an important role in cellular pathways, including cell cycle regulation, metabolism, differentiation and survival. The protein kinase superfamily network consists of 518 members involved in intrinsic or extrinsic interaction processes. Protein kinases are divided into two categories based on their ability to phosphorylate tyrosine, serine, and threonine residues. The complexity of the system implies its vulnerability. Any changes in the pathways of protein kinases may be implicated in pathological processes. Therefore, they are regarded as having an important role in human diseases and represent prospective therapeutic targets. This article provides a review of the protein kinase inhibitors approved by the FDA. Finally, we summarize the mechanism of action of protein kinases, including their role in the development and progression of protein kinase-related roles in various pathological conditions and the future therapeutic potential of protein kinase inhibitors, along with links to protein kinase databases. Further clinical studies aimed at examining the sequence of protein kinase inhibitor availability would better utilize current protein kinase inhibitors in diseases. Additionally, this review may help researchers and biochemists find new potent and selective protein kinase inhibitors and provide more indications for using existing drugs.</p></div>","PeriodicalId":793,"journal":{"name":"The Protein Journal","volume":"42 6","pages":"621 - 632"},"PeriodicalIF":3.0,"publicationDate":"2023-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41151891","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Investigating the Effect of Substituting a Single Cysteine Residue on the Thermal Stability of an Engineered Sweet Protein, Single-Chain Monellin 研究取代单一半胱氨酸残基对工程甜蛋白单链Monellin热稳定性的影响。

IF 3 4区生物学

The Protein Journal Pub Date : 2023-09-22 DOI: 10.1007/s10930-023-10154-0

Kyosuke Ohnuma, Atsuko Yamashita, Norihisa Yasui

{"title":"Investigating the Effect of Substituting a Single Cysteine Residue on the Thermal Stability of an Engineered Sweet Protein, Single-Chain Monellin","authors":"Kyosuke Ohnuma, Atsuko Yamashita, Norihisa Yasui","doi":"10.1007/s10930-023-10154-0","DOIUrl":"10.1007/s10930-023-10154-0","url":null,"abstract":"<div><p>Single-chain monellin (SCM) is an engineered protein that links the two chains of monellin, a naturally sweet-tasting protein. This protein is an attractive candidate for use as a sugar replacement in food and beverages and has numerous other applications. Therefore, generating SCM mutants with improved stability is an active area of research to broaden the range of its potential applications. In this study, we focused on the Cys41 residue of SCM, which is a single cysteine residue present at a structurally important position. This residue is often substituted with Ser. However, this substitution may destabilize SCM because Cys41 is buried in the hydrophobic core of the protein. Therefore, we designed mutants that substituted Ala, Val, and Leu for this residue, namely C41A, C41V, and C41L. We characterized these three mutants, SCM C41S, and wild type (WT). Differential scanning fluorimetric analysis revealed that substituting Cys41 with Ala or Val increased the thermal stability of SCM, while substitution with Ser or Leu decreased its stability. Determination of the crystal structures of SCM C41A and C41V mutants revealed that the overall structures and main chain structures around the 41st residue of both mutants were almost identical to the WT. On the other hand, the orientations of the amino acid side chains near the 41st residue differed among the SCM variants. Taken together, our results indicate that substituting Cys41 with Ala or Val increases the stability of SCM and provide insight into the structural basis of this improvement.</p></div>","PeriodicalId":793,"journal":{"name":"The Protein Journal","volume":"42 6","pages":"698 - 708"},"PeriodicalIF":3.0,"publicationDate":"2023-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s10930-023-10154-0.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41160982","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Biophysical Characterization of p51 and p66 Monomers of HIV-1 Reverse Transcriptase with Their Inhibitors HIV-1逆转录酶p51和p66单体及其抑制剂的生物物理特性。

IF 3 4区生物学

The Protein Journal Pub Date : 2023-09-20 DOI: 10.1007/s10930-023-10156-y

Supaphorn Seetaha, Nuntaporn Kamonsutthipaijit, Maho Yagi-Utsumi, Yanaka Seako, Takumi Yamaguchi, Supa Hannongbua, Koichi Kato, Kiattawee Choowongkomon

{"title":"Biophysical Characterization of p51 and p66 Monomers of HIV-1 Reverse Transcriptase with Their Inhibitors","authors":"Supaphorn Seetaha, Nuntaporn Kamonsutthipaijit, Maho Yagi-Utsumi, Yanaka Seako, Takumi Yamaguchi, Supa Hannongbua, Koichi Kato, Kiattawee Choowongkomon","doi":"10.1007/s10930-023-10156-y","DOIUrl":"10.1007/s10930-023-10156-y","url":null,"abstract":"<div><p>Human immunodeficiency virus (HIV)-1 reverse transcriptase (HIV-1 RT) is responsible for the transcription of viral RNA genomes into DNA genomes and has become an important target for the treatment of acquired immune deficiency syndrome (AIDS). This study used biophysical techniques to characterize the HIV-1 RT structure, monomer forms, and the non-nucleoside reverse transcriptase inhibitors (NNRTIs) bound forms. Inactive p66<sub>W401A</sub> and p51<sub>W401A</sub> were selected as models to study the HIV-1 RT monomer structures. Nuclear magnetic resonance (NMR) spectroscopy revealed that the unliganded forms of p66<sub>W401A</sub> protein and p51<sub>W401A</sub> protein had similar conformation to each other in solution. The complexes of p66<sub>W401A</sub> or p51<sub>W401A</sub> with inhibitors showed similar conformations to p66 in the RT heterodimer bound to the NNRTIs. Furthermore, the results of paramagnetic relaxation enhancement (PRE)-assisted NMR revealed that the unliganded forms of the p66<sub>W401A</sub> and p51<sub>W401A</sub> conformations were different from the unliganded heterodimer, characterized by a greater distance between the fingers and thumb subdomains. Small-angle X-ray scattering (SAXS) experiments confirmed that p66<sub>W401A</sub> and p51<sub>W401A</sub> can bind with inhibitors, similar to the p66/p51 heterodimer. The findings of this study increase the structural knowledge base of HIV-1 RT monomers, which may be helpful in the future design of potent viral inhibitors.</p></div>","PeriodicalId":793,"journal":{"name":"The Protein Journal","volume":"42 6","pages":"741 - 752"},"PeriodicalIF":3.0,"publicationDate":"2023-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41171873","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Analysis of a Novel Peptide That Is Capable of Inhibiting the Enzymatic Activity of the Protein Kinase A Catalytic Subunit-Like Protein from Trypanosoma equiperdum 一种能够抑制等锥虫蛋白激酶a催化亚基样蛋白酶活性的新型肽的分析。

IF 3 4区生物学

The Protein Journal Pub Date : 2023-09-15 DOI: 10.1007/s10930-023-10153-1

Nelson A. Araujo, José Bubis

{"title":"Analysis of a Novel Peptide That Is Capable of Inhibiting the Enzymatic Activity of the Protein Kinase A Catalytic Subunit-Like Protein from Trypanosoma equiperdum","authors":"Nelson A. Araujo, José Bubis","doi":"10.1007/s10930-023-10153-1","DOIUrl":"10.1007/s10930-023-10153-1","url":null,"abstract":"<div><p>A 26-residue peptide possessing the αN-helix motif of the protein kinase A (PKA) regulatory subunit-like proteins from the <i>Trypanozoom</i> subgenera (VAP26, sequence = VAPYFEKSEDETALILKLLTYNVLFS), was shown to inhibit the enzymatic activity of the <i>Trypanosoma equiperdum</i> PKA catalytic subunit-like protein, in a similar manner that the mammalian heat-stable soluble PKA inhibitor known as PKI. However, VAP26 does not contain the PKI inhibitory sequence. Bioinformatics analyzes of the αN-helix motif from various <i>Trypanozoon</i> PKA regulatory subunit-like proteins suggested that the sequence could form favorable peptide-protein interactions of hydrophobic nature with the PKA catalytic subunit-like protein, which possibly may represent an alternative PKA inhibitory mechanism. The sequence of the αN-helix motif of the <i>Trypanozoon</i> proteins was shown to be highly homologous but significantly divergent from the corresponding αN-helix motifs of their <i>Leishmania</i> and mammalian counterparts. This sequence divergence contrasted with the proposed secondary structure of the αN-helix motif, which appeared conserved in every analyzed regulatory subunit-like protein. In silico mutation experiments at positions I234, L238 and F244 of the αN-helix motif from the <i>Trypanozoon</i> proteins destabilized both the specific motif and the protein. On the contrary, mutations at positions T239 and Y240 stabilized the motif and the protein. These results suggested that the αN-helix motif from the <i>Trypanozoon</i> proteins probably possessed a different evolutionary path than their <i>Leishmania</i> and mammalian counterparts. Moreover, finding stabilizing mutations indicated that new inhibitory peptides may be designed based on the αN-helix motif from the <i>Trypanozoon</i> PKA regulatory subunit-like proteins.</p><h3>Graphical Abstract</h3>\u0000 <div><figure><div><div><picture><source><img></source></picture></div></div></figure></div>\u0000 </div>","PeriodicalId":793,"journal":{"name":"The Protein Journal","volume":"42 6","pages":"709 - 727"},"PeriodicalIF":3.0,"publicationDate":"2023-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10235912","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Development of a Chimeric Protein BiPPB-mIFNγ-tTβRII for Improving the Anti-Fibrotic Activity in Vivo by Targeting Fibrotic Liver and Dual Inhibiting the TGF-β1/Smad Signaling Pathway 嵌合蛋白BiPPB-mIFNγ-tTβRII的开发通过靶向纤维化肝和双重抑制TGF-β1/Smad信号通路来提高体内抗纤维化活性。

IF 3 4区生物学

The Protein Journal Pub Date : 2023-09-10 DOI: 10.1007/s10930-023-10147-z

Yixin Dong, Xiaohua Wang, Liming Xu, Xin Li, Haibing Dai, Xu Mao, Yanhui Chu, Xiaohuan Yuan, Haifeng Liu

{"title":"Development of a Chimeric Protein BiPPB-mIFNγ-tTβRII for Improving the Anti-Fibrotic Activity in Vivo by Targeting Fibrotic Liver and Dual Inhibiting the TGF-β1/Smad Signaling Pathway","authors":"Yixin Dong, Xiaohua Wang, Liming Xu, Xin Li, Haibing Dai, Xu Mao, Yanhui Chu, Xiaohuan Yuan, Haifeng Liu","doi":"10.1007/s10930-023-10147-z","DOIUrl":"10.1007/s10930-023-10147-z","url":null,"abstract":"<div><p>Excessive production of transforming growth factor β1 (TGF-β1) in activated hepatic stellate cells (aHSCs) promotes liver fibrosis by activating the TGF-β1/Smad signaling pathway. Thus, specifically inhibiting the pro-fibrotic activity of TGF-β1 in aHSCs is an ideal strategy for treating liver fibrosis. Overexpression of platelet-derived growth factor β receptor (PDGFβR) has been demonstrated on the surface of aHSCs relative to normal cells in liver fibrosis. Interferon-gamma peptidomimetic (mIFNγ) and truncated TGF-β receptor type II (tTβRII) inhibit the TGF-β1/Smad signaling pathway by different mechanisms. In this study, we designed a chimeric protein by the conjugation of (1) mIFNγ and tTβRII coupled via plasma protease-cleavable linker sequences (FNPKTP) to (2) PDGFβR-recognizing peptide (BiPPB), namely BiPPB-mIFNγ-tTβRII. This novel protein BiPPB-mIFNγ-tTβRII was effectively prepared using <i>Escherichia coli</i> expression system. The active components BiPPB-mIFNγ and tTβRII were slowly released from BiPPB-mIFNγ-tTβRII by hydrolysis using the plasma protease thrombin in vitro. Moreover, BiPPB-mIFNγ-tTβRII highly targeted to fibrotic liver tissues, markedly ameliorated liver morphology and fibrotic responses in chronic liver fibrosis mice by both inhibiting the phosphorylation of Smad2/3 and inducing the expression of Smad7. Meanwhile, BiPPB-mIFNγ-tTβRII markedly reduced the deposition of collagen fibrils and expression of fibrosis-related proteins in acute liver fibrosis mice. Furthermore, BiPPB-mIFNγ-tTβRII showed a good safety performance in both liver fibrosis mice. Taken together, BiPPB-mIFNγ-tTβRII improved the in vivo anti-liver fibrotic activity due to its high fibrotic liver-targeting potential and the dual inhibition of the TGF-β1/Smad signaling pathway, which may be a potential candidate for targeting therapy on liver fibrosis.</p></div>","PeriodicalId":793,"journal":{"name":"The Protein Journal","volume":"42 6","pages":"753 - 765"},"PeriodicalIF":3.0,"publicationDate":"2023-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10553259","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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