Biochemical Journal最新文献

Noncanonical RGS14 structural determinants control hormone-sensitive NPT2A-mediated phosphate transport. 非规范RGS14结构决定因素控制激素敏感的npt2a介导的磷酸盐运输。

IF 4.4 3区生物学

Biochemical Journal Pub Date : 2025-02-05 DOI: 10.1042/BCJ20240122

W Bruce Sneddon, Suneela Ramineni, G Emme Van Doorn, John R Hepler, Peter A Friedman

{"title":"Noncanonical RGS14 structural determinants control hormone-sensitive NPT2A-mediated phosphate transport.","authors":"W Bruce Sneddon, Suneela Ramineni, G Emme Van Doorn, John R Hepler, Peter A Friedman","doi":"10.1042/BCJ20240122","DOIUrl":"10.1042/BCJ20240122","url":null,"abstract":"The sodium phosphate cotransporter-2A (NPT2A) mediates basal and parathyroid hormone (PTH)- and fibroblast growth factor-23 (FGF23)-regulated phosphate transport in proximal tubule cells of the kidney. Both basal and hormone-sensitive transport require sodium hydrogen exchanger regulatory factor-1 (NHERF1), a scaffold protein with tandem PDZ domains, PDZ1 and PDZ2. NPT2A binds to PDZ1. RGS14 persistently represses hormone action by binding to PDZ2. The RGS14 canonical RGS domain, Ras/Rap-binding domains, and G protein regulatory motif cannot explain its regulatory effects on hormone-sensitive phosphate transport because these actions are mediated not only by the PTH receptor, a G protein-coupled receptor (GPCR), but also by the fibroblast growth factor receptor-1, a receptor tyrosine kinase that is not governed by G protein activity. Here, we identify the structural elements of RGS14 that mutually control the action of PTH and FGF23. RGS14 truncation constructs lacking upstream sequence and the RGS domain were fully functional. Removing the linker sequence between the RGS and RBD1 domains abolished RGS14 action. Examination of the α-helical linker region suggested candidate serine residues that might facilitate regulatory activities. RGS14 Ser266 and Ser269 are phosphorylated in response to PTH and FGF23, and replacement of these residues by Ala eliminated the actions of RGS14 on hormone-sensitive phosphate transport. PTH and FGF23 stimulated the phosphorylation of a peptide construct harboring the sites of purported phosphorylation and full-length RGS14. Mutating Ser266Ala and Ser269Ala abolished phosphorylation. The results establish that RGS14 regulation of phosphate transport requires targeted phosphorylation within the linker and an intact PDZ ligand.","PeriodicalId":8825,"journal":{"name":"Biochemical Journal","volume":" ","pages":"135-146"},"PeriodicalIF":4.4,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142943576","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Telomerase RNA evolution: a journey from plant telomeres to broader eukaryotic diversity.

IF 4.4 3区生物学

Biochemical Journal Pub Date : 2025-01-31 DOI: 10.1042/BCJ20240501

Petr Fajkus, Jiří Fajkus

{"title":"Telomerase RNA evolution: a journey from plant telomeres to broader eukaryotic diversity.","authors":"Petr Fajkus, Jiří Fajkus","doi":"10.1042/BCJ20240501","DOIUrl":"https://doi.org/10.1042/BCJ20240501","url":null,"abstract":"Telomeres, essential for maintaining genomic stability, are typically preserved through the action of telomerase, a ribonucleoprotein complex that synthesizes telomeric DNA. One of its two core components, telomerase RNA (TR), serves as the template for this synthesis, and its evolution across different species is both complex and diverse. This review discusses recent advancements in understanding TR evolution, with a focus on plants (Viridiplantae). Utilizing novel bioinformatic tools and accumulating genomic and transcriptomic data, combined with corresponding experimental validation, researchers have begun to unravel the intricate pathways of TR evolution and telomere maintenance mechanisms. Contrary to previous beliefs, a monophyletic origin of TR has been demonstrated first in land plants and subsequently across the broader phylogenetic megagroup Diaphoretickes. Conversely, the discovery of plant-type TRs in insects challenges assumptions about the monophyletic origin of TRs in animals, suggesting evolutionary innovations coinciding with arthropod divergence. The review also highlights key challenges in TR identification and provides examples of how these have been addressed. Overall, this work underscores the importance of expanding beyond model organisms to comprehend the full complexity of telomerase evolution, with potential applications in agriculture and biotechnology.","PeriodicalId":8825,"journal":{"name":"Biochemical Journal","volume":"482 3","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143070884","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Expanding the tagging toolbox for visualizing translation live.

IF 4.4 3区生物学

Biochemical Journal Pub Date : 2025-01-30 DOI: 10.1042/BCJ20240183

Rhiannon M Sears, Nathan L Nowling, Jake Yarbro, Ning Zhao

{"title":"Expanding the tagging toolbox for visualizing translation live.","authors":"Rhiannon M Sears, Nathan L Nowling, Jake Yarbro, Ning Zhao","doi":"10.1042/BCJ20240183","DOIUrl":"https://doi.org/10.1042/BCJ20240183","url":null,"abstract":"Translation is a highly regulated process that includes three steps: initiation, elongation, and termination. Tremendous efforts have been spent to study the regulation of each translation step. In the last two decades, researchers have begun to investigate translation by tracking it in its native and live intracellular environment with high spatiotemporal resolution. To achieve this goal, a handful of tagging tools have been developed that can distinguish nascent chains from previously synthesized mature proteins. In this review, we will focus on these tagging tools and describe their development, working mechanisms, and advantages and drawbacks in tracking translation in live mammalian cells and organisms. In the second part of the review, we will summarize novel discoveries in translation by a recently developed nascent polypeptide tracking technology using tandem epitope tag array tagging tools. The superior spatiotemporal resolution of this technology enables us to directly and continuously track nascent chains live and thus reveal preferred translation location and timing, as well as the kinetics of canonical and noncanonical translation, translation bursts, ribosome quality control, and nonsense-mediated mRNA decay. In the future, we expect more tagging tools to be developed that allow us to track other regulation processes of a protein, such as folding, modifications, and degradation. With the expanding tagging toolbox, there is potential that we can track a protein from translation to degradation to fully understand its regulation in a native live cell environment.","PeriodicalId":8825,"journal":{"name":"Biochemical Journal","volume":"482 3","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143070882","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The continued evolution of the L2 cephalosporinase in Stenotrophomonas maltophilia: a key driver of beta-lactam resistance. 嗜麦芽窄养单胞菌中L2头孢菌素酶的持续进化：β -内酰胺耐药性的关键驱动因素。

IF 4.4 3区生物学

Biochemical Journal Pub Date : 2025-01-30 DOI: 10.1042/BCJ20240478

Sylvia A Sapula, Yu Wang, Bradley J Hart, Jonathan J Whittall, Henrietta Venter

{"title":"The continued evolution of the L2 cephalosporinase in Stenotrophomonas maltophilia: a key driver of beta-lactam resistance.","authors":"Sylvia A Sapula, Yu Wang, Bradley J Hart, Jonathan J Whittall, Henrietta Venter","doi":"10.1042/BCJ20240478","DOIUrl":"10.1042/BCJ20240478","url":null,"abstract":"The Stenotrophomonas maltophilia L2 cephalosporinase is one of two beta-lactamases that afford S. maltophilia beta-lactam resistance. With the overuse of beta-lactams, selective pressures have contributed to the evolution of these proteins, generating proteins with an extended spectrum of activity. Variant L2 cephalosporinases have been detected, as has their distribution into two main clades (clades 1 and 2). Comprehensive analysis of six L2 variants, cloned into pET41a(+) and expressed in Escherichia coli BL21(DE3) cells, revealed that clade 1 variants exhibited higher ceftazidime resistance compared to clade 2. Notably, the Sm5341 L2 variant, carrying a Phe72Ile variation, displayed a significantly reduced resistance profile across all substrates tested, suggesting a key role of Phe72 in enzymatic activity. An Ile72Phe substitution in the pET41a(+) based Sm5341_L2 variant resulted in a gain-of-function for this protein, confirming the role of Phe72 in the activity of L2. Furthermore, residue interaction network analysis elucidated a pi-cation interaction between Tyr272 and Arg244, which may potentially be stabilizing the enzyme and its binding site. The presence of Tyr272 in clade 1 variants correlates with higher ceftazidime affinity, contrasting Asp272 in clade 2 variants. Displaying lower Km values and higher kcat/Km ratios, clade 1 L2 enzymes demonstrated a higher binding efficiency and greater catalytic efficiency for most of the substrates assessed. These results indicate that L2 enzymes are continuing to evolve and adapt to a selective environment fuelled by the overuse of beta-lactams. This adaptation may signal the beginning of an evolutionary process yielding variant L2 cephalosporinases with extended substrate profiles.","PeriodicalId":8825,"journal":{"name":"Biochemical Journal","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142969544","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Retraction: Regulation of BAD by cAMP-dependent protein kinase is mediated via phosphorylation of a novel site, Ser155.

IF 4.4 3区生物学

Biochemical Journal Pub Date : 2025-01-30 DOI: 10.1042/BJ3490547_RET

引用次数: 0

The C-terminal structure of the N6-methyladenosine deaminase YerA and its role in deamination.

IF 4.1 3区生物学

Biochemical Journal Pub Date : 2025-01-29 DOI: 10.1042/bcj20240728

Qian Jia,Hui Zeng,Nan Xiao,Jing Tang,Shangfang Gao,Wei Xie

{"title":"The C-terminal structure of the N6-methyladenosine deaminase YerA and its role in deamination.","authors":"Qian Jia,Hui Zeng,Nan Xiao,Jing Tang,Shangfang Gao,Wei Xie","doi":"10.1042/bcj20240728","DOIUrl":"https://doi.org/10.1042/bcj20240728","url":null,"abstract":"The N6-methyladenine (6mA) modification is an essential epigenetic marker and plays a crucial role in processes, such as DNA repair, replication, gene expression regulation, etc. YerA from Bacillus subtilis is considered a novel class of enzymes capable of catalyzing the deamination of 6mA to produce hypoxanthine. Despite the significance of this type of enzymes in bacterial self-defense systems and potential applications as a gene-editing tool, the substrate specificity, the catalytic mechanism and the physiological function of YerA are currently unclear due to the lack of structural information. In this study, we expressed the recombinant enzyme and conducted its reconstitution to yield the active form. Our deamination assays showed that N6-methyladenosine (N6-mAdo) served as a more favorable substrate than its base derivative 6mA. Here we report the high-resolution structure of the C-terminal region of YerA, which exhibited a compact architecture composed of two antiparallel b-sheets with no obvious close structural homologs in PDB. We also created docking models to investigate the ligand-binding pattern, and found that more favorable contacts of N6-mAdo with the enzyme binding pocket lead to its preference for 6mA. Lastly, structural comparison to the deaminase MAPDA allowed us to propose a plausible role for this C-terminal region: shielding the active site from solvent and protecting the intermediate during catalysis. Taken together, this study sheds light on the catalytic mechanism and evolutionary pathways of the promiscuous enzyme YerA, thereby contributing to our molecular understanding of epigenetic nucleoside metabolism.","PeriodicalId":8825,"journal":{"name":"Biochemical Journal","volume":"79 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143056730","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Structural and Kinetic Characterization of an Acetoacetyl-Coenzyme A: Acetate Coenzyme A Transferase from the Extreme Thermophile Thermosipho melanesiensis.

IF 4.4 3区生物学

Biochemical Journal Pub Date : 2025-01-27 DOI: 10.1042/BCJ20240747

Ryan G Bing, Greg K Buhrman, Kathryne C Ford, Christopher T Straub, Tunyaboon Laemthong, Robert B Rose, Michael Adams, Robert M Kelly

{"title":"Structural and Kinetic Characterization of an Acetoacetyl-Coenzyme A: Acetate Coenzyme A Transferase from the Extreme Thermophile Thermosipho melanesiensis.","authors":"Ryan G Bing, Greg K Buhrman, Kathryne C Ford, Christopher T Straub, Tunyaboon Laemthong, Robert B Rose, Michael Adams, Robert M Kelly","doi":"10.1042/BCJ20240747","DOIUrl":"https://doi.org/10.1042/BCJ20240747","url":null,"abstract":"CtfAB from the extremely thermophilic bacterium, Thermosipho melanesiensis, has been used for in vivo acetone production up to 70°C. This enzyme has tentatively been identified as the rate-limiting step, due to its relatively low binding affinity for acetate. However, existing kinetic and mechanistic studies on this enzyme are insufficient to evaluate this hypothesis. Here, kinetic analysis of purified recombinant T. melanesiensis CtfAB showed that it has a ping pong bi bi mechanism typical of CoA transferases with Km values for acetate and acetoacetyl-CoA of 85 mM and 135 mM, respectively. Product inhibition by acetyl-CoA was competitive with respect to acetoacetyl-CoA and non-competitive with respect to acetate. Crystal structures of wildtype and mutant T. melanesiensis CtfAB were solved in the presence of acetate and in the presence or absence of acetyl-CoA. These structures led to a proposed structural basis for the competitive and non-competitive inhibition of acetyl-CoA: acetate binds independently of acetyl-CoA in an apparent low affinity binding pocket in CtfA that is directly adjacent to a catalytic glutamate in CtfB. Similar to other CoA transferases, acetyl-CoA is bound in an apparent high affinity binding site in CtfB with most interactions occurring between the phospho-ADP of coenzyme A and CtfB residues far from the acetate binding pocket. This structural-based mechanism also explains the organic acid promiscuity of CtfAB. High affinity interactions are predominantly between the conserved phospho-ADP of coenzyme A and the variable organic acid binding site is a low affinity binding site with few specific interactions.","PeriodicalId":8825,"journal":{"name":"Biochemical Journal","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143051452","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Characterisation of RNA guanine-7 methyltransferase (RNMT) using a small molecule approach.

IF 4.4 3区生物学

Biochemical Journal Pub Date : 2025-01-27 DOI: 10.1042/BCJ20240608

Lesley-Anne Pearson, Alain-Pierre Petit, Cesar Mendoza-Martinez, Fiona Bellany, De Lin, Sarah Niven, Rachel Swift, Thomas Eadsforth, Paul K Fyfe, Marilyn Paul, Vincent Postis, Xiao Hu, Victoria H Cowling, David W Gray

{"title":"Characterisation of RNA guanine-7 methyltransferase (RNMT) using a small molecule approach.","authors":"Lesley-Anne Pearson, Alain-Pierre Petit, Cesar Mendoza-Martinez, Fiona Bellany, De Lin, Sarah Niven, Rachel Swift, Thomas Eadsforth, Paul K Fyfe, Marilyn Paul, Vincent Postis, Xiao Hu, Victoria H Cowling, David W Gray","doi":"10.1042/BCJ20240608","DOIUrl":"https://doi.org/10.1042/BCJ20240608","url":null,"abstract":"The maturation of the RNA cap involving guanosine N-7 methylation, catalyzed by the HsRNMT (RNA guanine-7 methyltransferase)-RAM (RNA guanine-N7 methyltransferase activating subunit) complex, is currently under investigation as a novel strategy to combat PIK3CA mutant breast cancer. However, the development of effective drugs is hindered by a limited understanding of the enzyme's mechanism and a lack of small molecule inhibitors. Following the elucidation of the HsRNMT-RAM molecular mechanism, we report the biophysical characterization of two small molecule hits. Biophysics, biochemistry and structural biology confirm that both compounds bind competitively with cap and bind effectively to HsRNMT-RAM in the presence of the co-product SAM, with a binding affinity (KD) of approximately 1 μM. This stabilisation of the enzyme-product complex results in uncompetitive inhibition. Finally, we describe the properties of the cap pocket and provided suggestions for further development of the tool compounds.","PeriodicalId":8825,"journal":{"name":"Biochemical Journal","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143051451","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Structure, kinetics, and mechanism of Pseudomonas putida sulfoquinovose dehydrogenase, the first enzyme in the sulfoglycolytic Entner-Doudoroff pathway.

IF 4.1 3区生物学

Biochemical Journal Pub Date : 2025-01-22 DOI: 10.1042/bcj20240605

Laura Burchill,Mahima Sharma,Niccolay Madiedo Soler,Ethan D Goddard-Borger,Gideon J Davies,Spencer J Williams

{"title":"Structure, kinetics, and mechanism of Pseudomonas putida sulfoquinovose dehydrogenase, the first enzyme in the sulfoglycolytic Entner-Doudoroff pathway.","authors":"Laura Burchill,Mahima Sharma,Niccolay Madiedo Soler,Ethan D Goddard-Borger,Gideon J Davies,Spencer J Williams","doi":"10.1042/bcj20240605","DOIUrl":"https://doi.org/10.1042/bcj20240605","url":null,"abstract":"The sulfosugar sulfoquinovose (SQ) is catabolized through the sulfoglycolytic Entner-Doudoroff pathway, beginning with the oxidation of SQ to sulfogluconolactone by SQ dehydrogenase. We present a comprehensive structural and kinetic characterization of Pseudomonas putida SQ dehydrogenase (PpSQDH). PpSQDH is a tetrameric enzyme belonging to the short-chain dehydrogenase/reductase (SDR) superfamily with a strong preference for NAD+ over NADP+. Kinetic analysis revealed a rapid equilibrium ordered mechanism in which the NAD+ cofactor is the first substrate to bind, and NADH is the last product to dissociate. Structural studies revealed a homotetrameric structure in solution and crystals, involving cross-subunit interactions in which the C-terminus residue (Gln260) inserts into the diagonally opposite subunit to form part of the second shell of residues lining the active site. Complexes of PpSQDH with SQ or NAD+ provide insight into the recognition of SQ and together with the kinetic analysis allow the proposal of a catalytic reaction mechanism. Our findings illuminate the mechanism of SQ degradation and the evolution of the SDR superfamily for organosulfonate catabolism.","PeriodicalId":8825,"journal":{"name":"Biochemical Journal","volume":"20 1","pages":"57-72"},"PeriodicalIF":4.1,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143056408","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Structural commonalities determined by physicochemical principles in the complex polymorphism of the amyloid state of proteins. 由物化原理决定的蛋白质淀粉样蛋白状态复杂多态性的结构共性。

IF 4.4 3区生物学

Biochemical Journal Pub Date : 2025-01-22 DOI: 10.1042/BCJ20240602

Silvia Errico, Giulia Fani, Salvador Ventura, Joost Schymkowitz, Frederic Rousseau, Antonio Trovato, Michele Vendruscolo, Francesco Bemporad, Fabrizio Chiti

{"title":"Structural commonalities determined by physicochemical principles in the complex polymorphism of the amyloid state of proteins.","authors":"Silvia Errico, Giulia Fani, Salvador Ventura, Joost Schymkowitz, Frederic Rousseau, Antonio Trovato, Michele Vendruscolo, Francesco Bemporad, Fabrizio Chiti","doi":"10.1042/BCJ20240602","DOIUrl":"10.1042/BCJ20240602","url":null,"abstract":"Advances in solid-state nuclear magnetic resonance (ssNMR) spectroscopy and cryogenic electron microscopy (cryoEM) have revealed the polymorphic nature of the amyloid state of proteins. Given the association of amyloid with protein misfolding disorders, it is important to understand the principles underlying this polymorphism. To address this problem, we combined computational tools to predict the specific regions of the sequence forming the β-spine of amyloid fibrils with the availability of 30, 83 and 24 amyloid structures deposited in the Protein Data Bank (PDB) and Amyloid Atlas (AAt) for the amyloid β (Aβ) peptide, α-synuclein (αS), and the 4R isoforms of tau, associated with Alzheimer's disease, Parkinson's disease, and various tauopathies, respectively. This approach enabled a statistical analysis of sequences forming β-sheet regions in amyloid polymorphs. We computed for any given sequence residue n the fraction of PDB/AAt structures in which that residue adopts a β-sheet conformation (Fβ(n)) to generate an experimental, structure-based profile of Fβ(n) vs n, which represents the β-conformational preference of any residue in the amyloid state. The peaks in the respective Fβ(n) profiles of the three proteins, corresponding to sequence regions adopting more frequently the β-sheet structural core in the various fibrillar structures, align very well with the peaks identified with five predictive algorithms (ZYGGREGATOR, TANGO, PASTA, AGGRESCAN, and WALTZ). These results indicate that, despite amyloid polymorphism, sequence regions most often forming the structural core of amyloid have high hydrophobicity, high intrinsic β-sheet propensity and low electrostatic charge across the sequence, as rationalised and predicted by the algorithms.","PeriodicalId":8825,"journal":{"name":"Biochemical Journal","volume":" ","pages":"87-101"},"PeriodicalIF":4.4,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142852315","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0