Biochimica et biophysica acta. Proteins and proteomics最新文献_第8页

Kinetic characterization of the N-terminal domain of Malonyl-CoA reductase 丙二酰-CoA 还原酶 N 端结构域的动力学特征

IF 3.2 4区生物学

Biochimica et biophysica acta. Proteins and proteomics Pub Date : 2023-12-18 DOI: 10.1016/j.bbapap.2023.140986

Mirela Tkalcic Cavuzic, Grover L. Waldrop

{"title":"Kinetic characterization of the N-terminal domain of Malonyl-CoA reductase","authors":"Mirela Tkalcic Cavuzic, Grover L. Waldrop","doi":"10.1016/j.bbapap.2023.140986","DOIUrl":"10.1016/j.bbapap.2023.140986","url":null,"abstract":"<div>Climate change is driving a search for environmentally safe methods to produce chemicals used in ordinary life. One such molecule is 3-hydroxypropionic acid, which is a platform industrial chemical used as a precursor for a variety of other chemical end products. The biosynthesis of 3-hydroxypropionic acid can be achieved in recombinant microorganisms via malonyl-CoA reductase in two separate reactions. The reduction of malonyl-CoA by NADPH to form malonic semialdehyde is catalyzed in the C-terminal domain of malonyl-CoA reductase, while the subsequent reduction of malonic semialdehyde to 3-hydroxypropionic acid is accomplished in the N-terminal domain of the enzyme. A new assay for the reverse reaction of the N-terminal domain of malonyl-CoA reductase from Chloroflexus aurantiacus activity has been developed. This assay was used to determine the kinetic mechanism and for isotope effect studies. Kinetic characterization using initial velocity patterns revealed random binding of the substrates NADP+ and 3-hydroxypropionic acid. Isotope effects showed substrates react to give products faster than they dissociate and that the products of the reverse reaction, NADPH and malonic semialdehyde, have a low affinity for the enzyme. Multiple isotope effects suggest proton and hydride transfer occur in a concerted fashion. This detailed kinetic characterization of the reaction catalyzed by the N-terminal domain of malonyl-CoA reductase could aid in engineering of the enzyme to make the biosynthesis of 3-hydroxypropionic acid commercially competitive with its production from fossil fuels.</div>","PeriodicalId":8760,"journal":{"name":"Biochimica et biophysica acta. Proteins and proteomics","volume":"1872 2","pages":"Article 140986"},"PeriodicalIF":3.2,"publicationDate":"2023-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138743316","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

Structural basis of nuclear transport for NEIL DNA glycosylases mediated by importin-alpha 由输入蛋白-α介导的 NEIL DNA 糖基化酶核运输的结构基础

IF 3.2 4区生物学

Biochimica et biophysica acta. Proteins and proteomics Pub Date : 2023-12-07 DOI: 10.1016/j.bbapap.2023.140974

Ivan R. Moraes , Hamine C. de Oliveira , Marcos R.M. Fontes

{"title":"Structural basis of nuclear transport for NEIL DNA glycosylases mediated by importin-alpha","authors":"Ivan R. Moraes , Hamine C. de Oliveira , Marcos R.M. Fontes","doi":"10.1016/j.bbapap.2023.140974","DOIUrl":"10.1016/j.bbapap.2023.140974","url":null,"abstract":"<div>NEIL glycosylases, including NEIL1, NEIL2, and NEIL3, play a crucial role in the base excision DNA repair pathway (BER). The classical importin pathway mediated by importin α/β and cargo proteins containing nuclear localization sequences (NLS) is the most common transport mechanism of DNA repair proteins to the nucleus. Previous studies have identified putative NLSs located at the C-terminus of NEIL3 and NEIL1. Crystallographic, bioinformatics, calorimetric (ITC), and fluorescence assays were used to investigate the interaction between NEIL1 and NEIL3 putative NLSs and importin-α (Impα). Our findings showed that NEIL3 contains a typical cNLS, with medium affinity for the major binding site of Impα. In contrast, crystallographic analysis of NEIL1 NLS revealed its binding to Impα, but with high B-factors and a lack of electron density at the linker region. ITC and fluorescence assays indicated no detectable affinity between NEIL1 NLS and Impα. These data suggest that NEIL1 NLS is a non-classical NLS with low affinity to Impα. Additionally, we compared the binding mode of NEIL3 and NEIL1 with Mus musculus Impα to human isoforms HsImpα1 and HsImpα3, which revealed interesting binding differences for HsImpα3 variant. NEIL3 is a classical medium affinity monopartite NLS, while NEIL1 is likely to be an unclassical low-affinity bipartite NLS. The base excision repair pathway is one of the primary systems involved in repairing DNA. Thus, understanding the mechanisms of nuclear transport of NEIL proteins is crucial for comprehending the role of these proteins in DNA repair and disease development.</div>","PeriodicalId":8760,"journal":{"name":"Biochimica et biophysica acta. Proteins and proteomics","volume":"1872 2","pages":"Article 140974"},"PeriodicalIF":3.2,"publicationDate":"2023-12-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138564206","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

Crystal structure and interconversion of monomers and domain-swapped dimers of the walnut tree phytocystatin 核桃树植物胱抑素单体和交换结构域二聚体的晶体结构和相互转化。

IF 3.2 4区生物学

Biochimica et biophysica acta. Proteins and proteomics Pub Date : 2023-12-04 DOI: 10.1016/j.bbapap.2023.140975

Gisele Alvarenga Simpson, Isabela Fernandes Rezende, Alencar da Silva Peixoto, Igor Barbosa de Oliveira Soares, João Alexandre Ribeiro Gonçalves Barbosa, Sônia Maria de Freitas, Napoleão Fonseca Valadares

{"title":"Crystal structure and interconversion of monomers and domain-swapped dimers of the walnut tree phytocystatin","authors":"Gisele Alvarenga Simpson, Isabela Fernandes Rezende, Alencar da Silva Peixoto, Igor Barbosa de Oliveira Soares, João Alexandre Ribeiro Gonçalves Barbosa, Sônia Maria de Freitas, Napoleão Fonseca Valadares","doi":"10.1016/j.bbapap.2023.140975","DOIUrl":"10.1016/j.bbapap.2023.140975","url":null,"abstract":"<div>Biotechnological applications of phytocystatins have garnered significant interest due to their potential applications in crop protection and improve crop resistance to abiotic stress factors. Cof1 and Wal1 are phytocystatins derived from Coffea arabica and Juglans regia, respectively. These plants hold significant economic value due to coffee's global demand and the walnut tree's production of valuable timber and widely consumed walnuts with culinary and nutritional benefits. The study involved the heterologous expression in E. coli Lemo 21(DE3), purification by immobilized metal ion affinity and size exclusion chromatography, and biophysical characterization of both phytocystatins, focusing on isolating and interconverting their monomers and dimers. The crystal structure of the domain-swapped dimer of Wal1 was determined revealing two domain-swapped dimers in the asymmetric unit, an arrangement reminiscent of the human cystatin C structure. Alphafold models of monomers and Alphafold-Multimer models of domain-swapped dimers of Cof1 and Wal1 were analyzed in the context of the crystal structure. The methodology and data presented here contribute to a deeper understanding of the oligomerization mechanisms of phytocystatins and their potential biotechnological applications in agriculture.</div>","PeriodicalId":8760,"journal":{"name":"Biochimica et biophysica acta. Proteins and proteomics","volume":"1872 2","pages":"Article 140975"},"PeriodicalIF":3.2,"publicationDate":"2023-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138497715","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

Paradoxical effects on ice nucleation are intrinsic to a small winter flounder antifreeze protein 对冰核的矛盾效应是固有的一个小的冬季比目鱼抗冻蛋白。

IF 3.2 4区生物学

Biochimica et biophysica acta. Proteins and proteomics Pub Date : 2023-11-11 DOI: 10.1016/j.bbapap.2023.140973

Xing Jian Chang , Dane C. Sands , Kathryn Vanya Ewart

{"title":"Paradoxical effects on ice nucleation are intrinsic to a small winter flounder antifreeze protein","authors":"Xing Jian Chang , Dane C. Sands , Kathryn Vanya Ewart","doi":"10.1016/j.bbapap.2023.140973","DOIUrl":"10.1016/j.bbapap.2023.140973","url":null,"abstract":"<div>Antifreeze proteins (AFPs) bind to ice in solutions, resulting in non-colligative freezing point depression; however, their effects on ice nucleation are not well understood. The predominant plasma AFP of winter flounder (Pseudopleuronectes americanus) is AFP6, which is an amphiphilic alpha helix. In this study, AFP6 and modified constructs were produced as fusion proteins in Escherichia coli, subjected to proteolysis when required and purified prior to use. AFP6 and its recombinant fusion precursor generated similar thermal hysteresis and bipyramidal ice crystals, whereas an inactive mutant AFP6 produced hexagonal crystals and no hysteresis. Circular dichroism spectra of the wild-type and mutant AFP6 were consistent with an alpha helix. The effects of these proteins on ice nucleation were investigated alongside non-AFP proteins using a standard droplet freezing assay. In the presence of nucleating AgI, modest reductions in the nucleation temperature occurred with the addition of mutant AFP6, and several non-AFPs, suggesting non-specific inhibition of AgI-induced ice nucleation. In these experiments, both AFP6 and its recombinant precursor resulted in lower nucleation temperatures, consistent with an additional inhibitory effect. Conversely, in the absence of AgI, AFP6 induced ice nucleation, with no other proteins showing this effect. Nucleation by AFP6 was dose-dependent, reaching a maximum at 1.5 mM protein. Nucleation by AFP6 also required an ice-binding site, as the inactive mutant had no effect. Furthermore, the absence of nucleation by the recombinant precursor protein suggested that the fusion moiety was interfering with the formation of a surface capable of nucleating ice.</div>","PeriodicalId":8760,"journal":{"name":"Biochimica et biophysica acta. Proteins and proteomics","volume":"1872 1","pages":"Article 140973"},"PeriodicalIF":3.2,"publicationDate":"2023-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"92152584","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

A dissected non-ribosomal peptide synthetase maintains activity 解剖的非核糖体肽合成酶保持活性。

IF 3.2 4区生物学

Biochimica et biophysica acta. Proteins and proteomics Pub Date : 2023-11-10 DOI: 10.1016/j.bbapap.2023.140972

Amanda J. Platt , Shae Padrick , Amy T. Ma , Joris Beld

引用次数: 0

Structural conservation in the glutathione binding in Sphingomonas sp. glutaredoxin Grx3 and variations for cold adaptation 鞘氨醇单胞菌谷胱甘肽结合的结构保守性。谷胱甘肽Grx3和冷适应变异。

IF 3.2 4区生物学

Biochimica et biophysica acta. Proteins and proteomics Pub Date : 2023-11-05 DOI: 10.1016/j.bbapap.2023.140971

Trang Van Tran, Hoa Nguyen, Luyen Vu, ChangWoo Lee

{"title":"Structural conservation in the glutathione binding in Sphingomonas sp. glutaredoxin Grx3 and variations for cold adaptation","authors":"Trang Van Tran, Hoa Nguyen, Luyen Vu, ChangWoo Lee","doi":"10.1016/j.bbapap.2023.140971","DOIUrl":"10.1016/j.bbapap.2023.140971","url":null,"abstract":"<div>Glutaredoxin 3 (Grx3), a redox protein with a thioredoxin-fold structure, maintains structural integrity and glutathione (GSH) binding capabilities across varying habitat temperatures. The cis-Pro loop, essential for GSH binding, relies on the Arg-Asp salt bridge (α2-α3) and Gln-His hydrogen bond (β3-β4) for its conformation. In some psychrophilic Grx3 variants, Arg in α2 is replaced with Tyr, and His in β4 is replaced with Phe. This study examines the roles of these bonds in Grx3's structure, function, and cold adaptation, using SpGrx3 from the Arctic bacterium Sphingomonas sp. Despite its cold habitat, SpGrx3 maintains the Arg51-Asp69 salt bridge and Gln56-His63 hydrogen bond. The R51Y substitution disrupts the α2-α3 salt bridge, while the H63F and H63Y substitutions hinder the salt bridge through cation-π interactions with Arg51, involving Phe63/Tyr63, thereby enhancing flexibility. Conversely, mutations that disrupt the hydrogen bond (Q56A, H63A, and H63F) reduce thermal stability. In the psychrophilic Grx3 configuration A48T/R51Y/H63F, a Thr48-Gln56 hydrogen bond stabilizes the cis-Pro loop, enhancing flexibility by disrupting both bonds. Furthermore, all mutants exhibit reduced α-helical content and catalytic efficiency. In summary, the highly conserved Arg51-Asp69 salt bridge and Gln56-His63 hydrogen bond are crucial for stabilizing the cis-Pro loop and catalytic activity in SpGrx3. His63 is favored as it avoids cation-π interactions with Arg51, unlike Phe63/Tyr63. Psychrophilic Grx3 variants have adapted to cold environments by reducing GSH binding and increasing structural flexibility. These findings deepen our understanding of the structural conservation in Grx3 for GSH binding and the critical alterations required for cold adaptation.</div>","PeriodicalId":8760,"journal":{"name":"Biochimica et biophysica acta. Proteins and proteomics","volume":"1872 1","pages":"Article 140971"},"PeriodicalIF":3.2,"publicationDate":"2023-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71477530","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

Structural characterization of the human DjC20/HscB cochaperone in solution 溶液中人DjC20/HscB辅酶A的结构表征。

IF 3.2 4区生物学

Biochimica et biophysica acta. Proteins and proteomics Pub Date : 2023-10-21 DOI: 10.1016/j.bbapap.2023.140970

Amanda Lais de Souza Coto , Arthur Alexandre Pereira , Sabrina Dorta Oliveira , Milene Nobrega de Oliveira Moritz , Arthur Moraes Franco da Rocha , Paulo Roberto Dores-Silva , Noeli Soares Melo da Silva , Ana Rita de Araújo Nogueira , Lisandra Marques Gava , Thiago Vagas Seraphim , Júlio César Borges

{"title":"Structural characterization of the human DjC20/HscB cochaperone in solution","authors":"Amanda Lais de Souza Coto , Arthur Alexandre Pereira , Sabrina Dorta Oliveira , Milene Nobrega de Oliveira Moritz , Arthur Moraes Franco da Rocha , Paulo Roberto Dores-Silva , Noeli Soares Melo da Silva , Ana Rita de Araújo Nogueira , Lisandra Marques Gava , Thiago Vagas Seraphim , Júlio César Borges","doi":"10.1016/j.bbapap.2023.140970","DOIUrl":"10.1016/j.bbapap.2023.140970","url":null,"abstract":"<div>J-domain proteins (JDPs) form a very large molecular chaperone family involved in proteostasis processes, such as protein folding, trafficking through membranes and degradation/disaggregation. JDPs are Hsp70 co-chaperones capable of stimulating ATPase activity as well as selecting and presenting client proteins to Hsp70. In mitochondria, human DjC20/HscB (a type III JDP that possesses only the conserved J-domain in some region of the protein) is involved in [FeS] protein biogenesis and assists human mitochondrial Hsp70 (HSPA9). Human DjC20 possesses a zinc-finger domain in its N-terminus, which closely contacts the J-domain and appears to be essential for its function. Here, we investigated the hDjC20 structure in solution as well as the importance of Zn+2 for its stability. The recombinant hDjC20 was pure, folded and capable of stimulating HSPA9 ATPase activity. It behaved as a slightly elongated monomer, as attested by small-angle X-ray scattering and SEC-MALS. The presence of Zn2+ in the hDjC20 samples was verified, a stoichiometry of 1:1 was observed, and its removal by high concentrations of EDTA and DTPA was unfeasible. However, thermal and chemical denaturation in the presence of EDTA led to a reduction in protein stability, suggesting a synergistic action between the chelating agent and denaturators that facilitate protein unfolding depending on metal removal. These data suggest that the affinity of Zn+2 for the protein is very high, evidencing its importance for the hDjC20 structure.</div>","PeriodicalId":8760,"journal":{"name":"Biochimica et biophysica acta. Proteins and proteomics","volume":"1872 1","pages":"Article 140970"},"PeriodicalIF":3.2,"publicationDate":"2023-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49688602","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

Protein interaction network revealed by quantitative proteomic analysis links TFIIB to multiple aspects of the transcription cycle 定量蛋白质组学分析揭示的蛋白质相互作用网络将TFIIB与转录周期的多个方面联系起来。

IF 3.2 4区生物学

Biochimica et biophysica acta. Proteins and proteomics Pub Date : 2023-10-19 DOI: 10.1016/j.bbapap.2023.140968

Michael J. O'Brien, Athar Ansari

{"title":"Protein interaction network revealed by quantitative proteomic analysis links TFIIB to multiple aspects of the transcription cycle","authors":"Michael J. O'Brien, Athar Ansari","doi":"10.1016/j.bbapap.2023.140968","DOIUrl":"10.1016/j.bbapap.2023.140968","url":null,"abstract":"<div>Although TFIIB is widely regarded as an initiation factor, recent reports have implicated it in multiple aspects of eukaryotic transcription. To investigate the broader role of TFIIB in transcription, we performed quantitative proteomic analysis of yeast TFIIB. We purified two different populations of TFIIB; one from soluble cell lysate, which is not engaged in transcription, and the other from the chromatin fraction which yields the transcriptionally active form of the protein. TFIIB purified from the chromatin exhibits several interactions that explain its non-canonical roles in transcription. RNAPII, TFIIF and TFIIH were the only components of the preinitiation complex with a significant presence in chromatin TFIIB. A notable feature was enrichment of all subunits of CF1 and Rat1 3′ end processing-termination complexes in chromatin-TFIIB preparation. Subunits of the CPF termination complex were also detected in both chromatin and soluble derived TFIIB preparations. These results may explain the presence of TFIIB at the 3′ end of genes during transcription as well as its role in promoter-termination interaction.</div>","PeriodicalId":8760,"journal":{"name":"Biochimica et biophysica acta. Proteins and proteomics","volume":"1872 1","pages":"Article 140968"},"PeriodicalIF":3.2,"publicationDate":"2023-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49673830","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

Structure of the Borrelia burgdorferi ATP-dependent metalloprotease FtsH in its functionally relevant hexameric form 伯氏疏螺旋体ATP依赖性金属蛋白酶FtsH的结构，其功能相关的六聚体形式。

IF 3.2 4区生物学

Biochimica et biophysica acta. Proteins and proteomics Pub Date : 2023-10-16 DOI: 10.1016/j.bbapap.2023.140969

Kalvis Brangulis , Laura Drunka , Inara Akopjana , Kaspars Tars

{"title":"Structure of the Borrelia burgdorferi ATP-dependent metalloprotease FtsH in its functionally relevant hexameric form","authors":"Kalvis Brangulis , Laura Drunka , Inara Akopjana , Kaspars Tars","doi":"10.1016/j.bbapap.2023.140969","DOIUrl":"10.1016/j.bbapap.2023.140969","url":null,"abstract":"<div>ATP-dependent proteases FtsH are conserved in bacteria, mitochondria, and chloroplasts, where they play an essential role in degradation of misfolded/unneeded membrane and cytosolic proteins. It has also been demonstrated that the FtsH homologous protein BB0789 is crucial for mouse and tick infectivity and in vitro growth of the Lyme disease-causing agent Borrelia burgdorferi. This is not surprising, considering B. burgdorferi complex life cycle, residing in both in mammals and ticks, which requires a wide range of membrane proteins and short-lived cytosolic regulatory proteins to invade and persist in the host organism.In the current study, we have solved the crystal structure of the cytosolic BB0789166–614, lacking both N-terminal transmembrane α-helices and the small periplasmic domain. The structure revealed the arrangement of the AAA+ ATPase and the zinc-dependent metalloprotease domains in a hexamer ring, which is essential for ATPase and proteolytic activity. The AAA+ domain was found in an ADP-bound state, while the protease domain showed coordination of a zinc ion by two histidine residues and one aspartic acid residue. The loop region that forms the central pore in the oligomer was poorly defined in the crystal structure and therefore predicted by AlphaFold to complement the missing structural details, providing a complete picture of the functionally relevant hexameric form of BB0789. We confirmed that BB0789 is functionally active, possessing both protease and ATPase activities, thus providing novel structural-functional insights into the protein, which is known to be absolutely necessary for B. burgdorferi to survive and cause Lyme disease.</div>","PeriodicalId":8760,"journal":{"name":"Biochimica et biophysica acta. Proteins and proteomics","volume":"1872 1","pages":"Article 140969"},"PeriodicalIF":3.2,"publicationDate":"2023-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49673831","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

Antibodies and α-synuclein: What to target against Parkinson's Disease? 抗体和α-突触核蛋白：针对帕金森病的靶点是什么？

IF 3.2 4区生物学

Biochimica et biophysica acta. Proteins and proteomics Pub Date : 2023-09-30 DOI: 10.1016/j.bbapap.2023.140943

Daniel E. Otzen

{"title":"Antibodies and α-synuclein: What to target against Parkinson's Disease?","authors":"Daniel E. Otzen","doi":"10.1016/j.bbapap.2023.140943","DOIUrl":"10.1016/j.bbapap.2023.140943","url":null,"abstract":"<div>Parkinson's Disease (PD) is strongly linked to the aggregation of the protein α-synuclein (α-syn), an intrinsically disordered protein. However, strategies to combat PD by targeting the aggregation of α-syn are challenged by the multiple types of aggregates formed both in vivo and in vitro, the potential influence of chemical modifications and the as yet unresolved question of which aggregate types (oligomeric or fibrillar) are most cytotoxic. Here I briefly review the social history of α-syn, the many efforts to raise antibodies against α-syn and the disappointing results of clinical trials based on such antibodies. Ultimately a thorough understanding of the molecular and mechanistic properties of mAbs towards aggregated species of α-syn is an essential prerequisite for any clinical trial, but this is missing in most cases. I highlight new microfluidic techniques which may address this need and call for a more concerted effort to standardize antibody studies as the basis to allow us to link molecular insights to clinical efficacy.</div>","PeriodicalId":8760,"journal":{"name":"Biochimica et biophysica acta. Proteins and proteomics","volume":"1872 2","pages":"Article 140943"},"PeriodicalIF":3.2,"publicationDate":"2023-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1570963923000572/pdfft?md5=f552b3b8ed7908aa2862434b374887f3&pid=1-s2.0-S1570963923000572-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41123165","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