Biochimica et biophysica acta. Proteins and proteomics最新文献

{"title":"Human apo-metallothionein 1a is not a random coil: Evidence from guanidinium chloride, high temperature, and acidic pH unfolding studies","authors":"Natalie C. Korkola,&nbsp;Martin J. Stillman","doi":"10.1016/j.bbapap.2024.141010","DOIUrl":"10.1016/j.bbapap.2024.141010","url":null,"abstract":"<div><p>The structures of apo-metallothioneins (apo-MTs) have been relatively elusive due to their fluxional, disordered state which has been difficult to characterize. However, intrinsically disordered protein (IDP) structures are rather diverse, which raises questions about where the structure of apo-MTs fit into the protein structural spectrum. In this paper, the unfolding transitions of apo-MT1a are discussed with respect to the effect of the chemical denaturant GdmCl, temperature conditions, and pH environment. Cysteine modification in combination with electrospray ionization mass spectrometry was used to probe the unfolding transition of apo-MT1a in terms of cysteine exposure. Circular dichroism spectroscopy was also used to monitor the change in secondary structure as a function of GdmCl concentration. For both of these techniques, cooperative unfolding was observed, suggesting that apo-MT1a is not a random coil. More GdmCl was required to unfold the protein backbone than to expose the cysteines, indicating that cysteine exposure is likely an early step in the unfolding of apo-MT1a. MD simulations complement the experimental results, suggesting that apo-MT1a adopts a more compact structure than expected for a random coil. Overall, these results provide further insight into the intrinsically disordered structure of apo-MT.</p></div>","PeriodicalId":8760,"journal":{"name":"Biochimica et biophysica acta. Proteins and proteomics","volume":"1872 4","pages":"Article 141010"},"PeriodicalIF":3.2,"publicationDate":"2024-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1570963924000177/pdfft?md5=1e2b99a81d2977a21cf2abac24f96759&pid=1-s2.0-S1570963924000177-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140136421","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}

{"title":"Structural basis for the allosteric behaviour and substrate specificity of Lactococcus lactis Prolidase","authors":"Shangyi Xu ,&nbsp;Pawel Grochulski ,&nbsp;Takuji Tanaka","doi":"10.1016/j.bbapap.2024.141000","DOIUrl":"10.1016/j.bbapap.2024.141000","url":null,"abstract":"<div><p>Prolidase (EC 3.4.13.9) is an enzyme that specifically hydrolyzes Xaa-Pro dipeptides into free amino acids. We previously studied kinetic behaviours and solved the crystal structure of wild-type (WT) <em>Lactococcus lactis</em> prolidase (<em>Ll</em>prol), showing that this homodimeric enzyme has unique characteristics: allosteric behaviour and substrate inhibition. In this study, we focused on solving the crystal structures of three <em>Ll</em>prol mutants (D36S, H38S, and R293S) which behave differently in <em>v</em>-<em>S</em> plots. The D36S and R293S <em>Ll</em>prol mutants do not show allosteric behaviour, and the <em>Ll</em>prol mutant H38S has allosteric behaviour comparable to the WT enzyme (Hill constant 1.52 and 1.58, respectively). The crystal structures of <em>Ll</em>prol variants suggest that the active site of <em>Ll</em>prol formed with amino acid residues from both monomers, <em>i.e.</em>, located in an interfacial area of dimer. The comparison between the structure models of <em>Ll</em>prol indicated that the two monomers in the dimers of <em>Ll</em>prol variants have different relative positions among <em>Ll</em>prol variants. They showed different interatomic distances between the amino acid residues bridging the two monomers and varied sizes of the solvent-accessible interface areas in each <em>Ll</em>prol variant. These observations indicated that <em>Ll</em>prol could adapt to different conformational states with distinctive substrate affinities. It is strongly speculated that the domain movements required for productive substrate binding are restrained in allosteric <em>Ll</em>prol (WT and H38S). At low substrate concentrations, only one out of the two active sites at the dimer interface could accept substrate; as a result, the asymmetrical activated dimer leads to allosteric behaviour.</p></div>","PeriodicalId":8760,"journal":{"name":"Biochimica et biophysica acta. Proteins and proteomics","volume":"1872 3","pages":"Article 141000"},"PeriodicalIF":3.2,"publicationDate":"2024-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1570963924000074/pdfft?md5=91ed69605856a30f112d2ccce3c18f91&pid=1-s2.0-S1570963924000074-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139464125","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}

{"title":"Biophysical characterization of human-cell-expressed, full-length κI O18/O8, AL-09, λ6a, and Wil immunoglobulin light chains","authors":"Pinaki Misra ,&nbsp;Alexander Tischer ,&nbsp;Lindsey Lampe ,&nbsp;Valeria Pierluissi-Ruiz ,&nbsp;Christopher J. Dick ,&nbsp;Benoit Bragantini ,&nbsp;Nikita Kormshchikov ,&nbsp;Matthew Auton ,&nbsp;Marina Ramirez-Alvarado","doi":"10.1016/j.bbapap.2023.140993","DOIUrl":"10.1016/j.bbapap.2023.140993","url":null,"abstract":"<div><p>Immunoglobulin light chain (AL) amyloidosis involves the deposition of insoluble monoclonal AL protein fibrils in the extracellular space of different organs leading to dysfunction and death. Development of methods to efficiently express and purify AL proteins with acceptable standards of homogeneity and structural integrity has become critical to understand the in vitro and in vivo aspects of AL protein aggregation, and thus the disease progression. In this study, we report the biophysical characterization of His-tagged and untagged versions of AL full-length (FL) κI and λ6 subgroup proteins and their mutants expressed from the Expi293F human cell line. We used an array of biophysical and biochemical methods to analyze the structure and stability of the monomers<span>, oligomerization<span> states, and thermodynamic characteristics of the purified FL proteins and how they compare with the bacterially expressed FL proteins. Our results demonstrate that the tagged and untagged versions of FL proteins have comparable stability to proteins expressed in bacterial cells but exhibit multiple unfolding transitions and reversibility. Non-reducing SDS-PAGE and analytical ultracentrifugation<span> analysis showed presence of monomers and dimers, with an insignificant amount of higher-order oligomers<span>, in the purified fraction of all proteins. Overall, the FL proteins were expressed with sufficient yields for biophysical studies and can replace bacterial expression systems.</span></span></span></span></p></div>","PeriodicalId":8760,"journal":{"name":"Biochimica et biophysica acta. Proteins and proteomics","volume":"1872 3","pages":"Article 140993"},"PeriodicalIF":3.2,"publicationDate":"2023-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139078691","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}

{"title":"Characterisation of the forest cobra (Naja melanoleuca) venom using a multifaceted mass spectrometric-based approach","authors":"C. Ruth Wang ,&nbsp;Alix C. Harlington ,&nbsp;Marten F. Snel ,&nbsp;Tara L. Pukala","doi":"10.1016/j.bbapap.2023.140992","DOIUrl":"10.1016/j.bbapap.2023.140992","url":null,"abstract":"<div><p>Snake venoms consist of highly biologically active proteins and peptides that are responsible for the lethal physiological effects of snakebite envenomation. In order to guide the development of targeted antivenom strategies, comprehensive understanding of venom compositions and in-depth characterisation of various proteoforms, often not captured by traditional bottom-up proteomic workflows, is necessary. Here, we employ an integrated ‘omics’ and intact mass spectrometry (MS)-based approach to profile the heterogeneity within the venom of the forest cobra (<em>Naja melanoleuca</em>), adopting different analytical strategies to accommodate for the dynamic molecular mass range of venom proteins present. The venom proteome of <em>N. melanoleuca</em> was catalogued using a venom gland transcriptome-guided bottom-up proteomics approach, revealing a venom consisting of six toxin superfamilies. The subtle diversity present in the venom components was further explored using reversed phase-ultra performance liquid chromatography (RP-UPLC) coupled to intact MS. This approach showed a significant increase in the number of venom proteoforms within various toxin families that were not captured in previous studies. Furthermore, we probed at the higher-order structures of the larger venom proteins using a combination of native MS and mass photometry and revealed significant structural heterogeneity along with extensive post-translational modifications in the form of glycosylation in these larger toxins. Here, we show the diverse structural heterogeneity of snake venom proteins in the venom of <em>N. melanoleuca</em> using an integrated workflow that incorporates analytical strategies that profile snake venom at the proteoform level, complementing traditional venom characterisation approaches.</p></div>","PeriodicalId":8760,"journal":{"name":"Biochimica et biophysica acta. Proteins and proteomics","volume":"1872 2","pages":"Article 140992"},"PeriodicalIF":3.2,"publicationDate":"2023-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1570963923001061/pdfft?md5=9f90ffa18983755cb88a42ffd1e66236&pid=1-s2.0-S1570963923001061-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139053420","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}

{"title":"Methionine gamma lyase: Structure-activity relationships and therapeutic applications","authors":"Samanta Raboni ,&nbsp;Serena Faggiano ,&nbsp;Stefano Bettati ,&nbsp;Andrea Mozzarelli","doi":"10.1016/j.bbapap.2023.140991","DOIUrl":"10.1016/j.bbapap.2023.140991","url":null,"abstract":"<div><p>Methionine gamma lyase (MGL) is a bacterial and plant enzyme that catalyzes the conversion of methionine in methanthiol, 2-oxobutanoate and ammonia. The enzyme belongs to fold type I of the pyridoxal 5′-dependent family. The catalytic mechanism and the structure of wild type MGL and variants were determined in the presence of the natural substrate as well as of many sulfur-containing derivatives. Structure-function relationship studies were pivotal for MGL exploitation in the treatment of cancer, bacterial infections, and other diseases. MGL administration to cancer cells leads to methionine starvation, thus decreasing cells viability and increasing their vulnerability towards other drugs. In antibiotic therapy, MGL acts by transforming prodrugs in powerful drugs. Numerous strategies have been pursued for the delivering of MGL <em>in vivo</em> to prolong its bioavailability and decrease its immunogenicity. These include conjugation with polyethylene glycol and encapsulation in synthetic or natural vesicles, eventually decorated with tumor targeting molecules, such as the natural phytoestrogens daidzein and genistein. The scientific achievements in studying MGL structure, function and perspective therapeutic applications came from the efforts of many talented scientists, among which late Tatyana Demidkina to whom we dedicate this review.</p></div>","PeriodicalId":8760,"journal":{"name":"Biochimica et biophysica acta. Proteins and proteomics","volume":"1872 3","pages":"Article 140991"},"PeriodicalIF":3.2,"publicationDate":"2023-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S157096392300105X/pdfft?md5=11f3b51520c4e2011e3a75effed6de51&pid=1-s2.0-S157096392300105X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139036583","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}

{"title":"Propagation of conformational instability in FK506-binding protein FKBP12","authors":"David M. LeMaster,&nbsp;Qamar Bashir,&nbsp;Griselda Hernández","doi":"10.1016/j.bbapap.2023.140990","DOIUrl":"10.1016/j.bbapap.2023.140990","url":null,"abstract":"<div><p>FKBP12 is the archetype of the FK506 binding domains that define the family of FKBP proteins which participate in the regulation of various distinct physiological signaling processes. As the drugs FK506 and rapamycin inhibit many of these FKBP proteins, there is need to develop therapeutics which exhibit selectivity within this family. The long β₄-β₅ loop of the FKBP domain is known to regulate transcriptional activity for the steroid hormone receptors and appears to participate in regulating calcium channel activity for the cardiac and skeletal muscle ryanodine receptors. The β₄-β₅ loop of FKBP12 has been shown to undergo extensive conformational dynamics, and here we report hydrogen exchange measurements for a series of mutational variants in that loop which indicate deviations from a two-state kinetics for those dynamics. In addition to a previously characterized local transition near the tip of this loop, evidence is presented for a second site of conformational dynamics in the stem of this loop. These mutation-dependent hydrogen exchange effects extend beyond the β₄-β₅ loop, primarily by disrupting the hydrogen bond between the Gly 58 amide and the Tyr 80 carbonyl oxygen which links the two halves of the structural rim that surrounds the active site cleft. Mutationally-induced opening of the cleft between Gly 58 and Tyr 80 not only modulates the global stability of the protein, it promotes a conformational transition in the distant β₂-β_3a hairpin that modulates the binding affinity for a FKBP51-selective inhibitor previously designed to exploit a localized conformational transition at the homologous site.</p></div>","PeriodicalId":8760,"journal":{"name":"Biochimica et biophysica acta. Proteins and proteomics","volume":"1872 3","pages":"Article 140990"},"PeriodicalIF":3.2,"publicationDate":"2023-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1570963923001048/pdfft?md5=91c5189e8a05670fa77c5412b345dfc4&pid=1-s2.0-S1570963923001048-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139029115","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}

{"title":"PDZome-wide and structural characterization of the PDZ-binding motif of VANGL2","authors":"Marta Montserrat-Gomez ,&nbsp;Gergo Gogl ,&nbsp;Kendall Carrasco ,&nbsp;Stephane Betzi ,&nbsp;Fabien Durbesson ,&nbsp;Alexandra Cousido-Siah ,&nbsp;Camille Kostmann ,&nbsp;Dominic J. Essig ,&nbsp;Kristian Strømgaard ,&nbsp;Søren Østergaard ,&nbsp;Xavier Morelli ,&nbsp;Gilles Trave ,&nbsp;Renaud Vincentelli ,&nbsp;Eric Bailly ,&nbsp;Jean-Paul Borg","doi":"10.1016/j.bbapap.2023.140989","DOIUrl":"10.1016/j.bbapap.2023.140989","url":null,"abstract":"<div><p>VANGL2 is a core component of the non-canonical Wnt/Planar Cell Polarity<span><span> signaling pathway<span> that uses its highly conserved carboxy-terminal type 1 PDZ-binding motif (PBM) to bind a variety of PDZ proteins. In this study, we characterize and quantitatively assess the largest VANGL2 PDZome-binding profile documented so far, using orthogonal methods. The results of our holdup approach support VANGL2 interactions with a large panel of both long-recognized and unprecedented PDZ domains<span>. Truncation and point mutation<span> analyses of the VANGL2 PBM establish that, beyond the strict requirement of the P-0 / V521 and P-2 / T519 amino acids, upstream residues, including E518, Q516 and R514 at, respectively, P-3, P-5 and P-7 further contribute to the robustness of VANGL2 interactions with two distinct PDZ domains, </span></span></span></span>SNX27 and SCRIBBLE-PDZ3. In agreement with these data, incremental amino-terminal deletions of the VANGL2 PBM causes its overall affinity to progressively decline. Moreover, the holdup data establish that the PDZome binding repertoire of VANGL2 starts to diverge significantly with the truncation of E518. A structural analysis of the SYNJ2BP-PDZ/VANGL2 interaction with truncated PBMs identifies a major conformational change in the binding direction of the PBM peptide after the P-2 position. Finally, we report that the PDZome binding profile of VANGL2 is dramatically rearranged upon phosphorylation of S517, T519 and S520. Our crystallographic approach illustrates how SYNJ2BP accommodates a S520-phosphorylated PBM peptide through the ideal positioning of two basic residues, K48 and R86. Altogether our data provides a comprehensive view of the VANGL2 PDZ network and how this network specifically responds to the post-translation modification of distinct PBM residues. These findings should prove useful in guiding future functional and molecular studies of the key PCP component VANGL2.</span></p></div>","PeriodicalId":8760,"journal":{"name":"Biochimica et biophysica acta. Proteins and proteomics","volume":"1872 3","pages":"Article 140989"},"PeriodicalIF":3.2,"publicationDate":"2023-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139032141","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}

{"title":"BthTX-I, a phospholipase A2-like toxin, is inhibited by the plant cinnamic acid derivative: chlorogenic acid","authors":"Fábio Florença Cardoso ,&nbsp;Guilherme Henrique Marchi Salvador ,&nbsp;Walter Luís Garrido Cavalcante ,&nbsp;Maeli Dal-Pai ,&nbsp;Marcos Roberto de Mattos Fontes","doi":"10.1016/j.bbapap.2023.140988","DOIUrl":"10.1016/j.bbapap.2023.140988","url":null,"abstract":"<div><p>Snakebite is a significant health concern in tropical and subtropical regions, particularly in Africa, Asia, and Latin America, resulting in more than 2.7 million envenomations and an estimated one hundred thousand fatalities annually. The <span><em>Bothrops</em></span><span> genus is responsible for the majority of snakebite envenomings in Latin America and Caribbean countries. Accidents involving snakes from this genus are characterized by local symptoms that often lead to permanent sequelae and death. However, specific antivenoms exhibit limited effectiveness in inhibiting local tissue damage. Phospholipase A</span>₂-like (PLA₂-like) toxins emerge as significant contributors to local myotoxicity in accidents involving <em>Bothrops</em> species. As a result, they represent a crucial target for prospective treatments. Some natural and synthetic compounds have shown the ability to reduce or abolish the myotoxic effects of PLA₂<span>-like proteins. In this study, we employed a combination approach involving myographic, morphological, biophysical and bioinformatic techniques to investigate the interaction between chlorogenic acid (CGA) and BthTX-I, a PLA</span>₂<span>-like toxin. CGA provided a protection of 71.8% on muscle damage in a pre-incubation treatment. Microscale thermophoresis and circular dichroism<span><span> experiments revealed that CGA interacted with the BthTX-I while preserving its secondary structure. CGA exhibited an affinity to the toxin that ranks among the highest observed for a </span>natural compound<span>. Bioinformatics simulations indicated that CGA inhibitor binds to the toxin's hydrophobic channel in a manner similar to other phenolic compounds previously investigated. These findings suggest that CGA interferes with the allosteric transition of the non-activated toxin, and the stability of the dimeric assembly of its activated state.</span></span></span></p></div>","PeriodicalId":8760,"journal":{"name":"Biochimica et biophysica acta. Proteins and proteomics","volume":"1872 2","pages":"Article 140988"},"PeriodicalIF":3.2,"publicationDate":"2023-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139020605","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}

{"title":"FunPredCATH: An ensemble method for predicting protein function using CATH","authors":"Joseph Bonello ,&nbsp;Christine Orengo","doi":"10.1016/j.bbapap.2023.140985","DOIUrl":"10.1016/j.bbapap.2023.140985","url":null,"abstract":"<div><h3>Motivation</h3><p>The growth of unannotated proteins in UniProt increases at a very high rate every year due to more efficient sequencing methods. However, the experimental annotation of proteins is a lengthy and expensive process. Using computational techniques to narrow the search can speed up the process by providing highly specific Gene Ontology (GO) terms.</p></div><div><h3>Methodology</h3><p>We propose an ensemble approach that combines three generic base predictors that predict Gene Ontology (BP, CC and MF) terms from sequences across different species. We train our models on UniProtGOA annotation data and use the CATH domain resources to identify the protein families. We then calculate a score based on the prevalence of individual GO terms in the functional families that is then used as an indicator of confidence when assigning the GO term to an uncharacterised protein.</p></div><div><h3>Methods</h3><p>In the ensemble, we use a statistics-based method that scores the occurrence of GO terms in a CATH FunFam against a background set of proteins annotated by the same GO term. We also developed a set-based method that uses Set Intersection and Set Union to score the occurrence of GO terms within the same CATH FunFam. Finally, we also use FunFams-Plus, a predictor method developed by the Orengo Group at UCL to predict GO terms for uncharacterised proteins in the CAFA3 challenge.</p></div><div><h3>Evaluation</h3><p>We evaluated the methods against the CAFA3 benchmark and DomFun. We used the Precision, Recall and F_max metrics and the benchmark datasets that are used in CAFA3 to evaluate our models and compare them to the CAFA3 results. Our results show that FunPredCATH compares well with top CAFA methods in the different ontologies and benchmarks.</p></div><div><h3>Contributions</h3><p>FunPredCATH compares well with other prediction methods on CAFA3, and the ensemble approach outperforms the base methods. We show that non-IEA models obtain higher F_max scores than the IEA counterparts, while the models including IEA annotations have higher coverage at the expense of a lower F_max score.</p></div>","PeriodicalId":8760,"journal":{"name":"Biochimica et biophysica acta. Proteins and proteomics","volume":"1872 2","pages":"Article 140985"},"PeriodicalIF":3.2,"publicationDate":"2023-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1570963923000997/pdfft?md5=0f4fa65f8e4df32c9a5a9a3d8e17897f&pid=1-s2.0-S1570963923000997-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138743449","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}

{"title":"Classification of binding property of amyloid β to lipid membranes: Membranomic research using quartz crystal microbalance combined with the immobilization of lipid planar membranes","authors":"Toshinori Shimanouchi ,&nbsp;Miki Iwamura ,&nbsp;Yasuhiro Sano ,&nbsp;Keita Hayashi ,&nbsp;Minoru Noda ,&nbsp;Yukitaka Kimura","doi":"10.1016/j.bbapap.2023.140987","DOIUrl":"10.1016/j.bbapap.2023.140987","url":null,"abstract":"<div><p><span><span><span>A biomembrane-related fibrillogenesis of </span>Amyloid β from Alzheimer’ disease (Aβ) is closely related to its accumulation behavior. A binding property of Aβ peptides from Alzheimer’ disease to </span>lipid membranes was then classified by a quartz crystal microbalance (QCM) method combined with an immobilization technique using thiol self-assembled membrane. The accumulated amounts of Aβ, Δ</span><em>f</em>_max, was determined from the measurement of the maximal frequency reduction using QCM. The plots of Δ<em>f</em>_max to Aβ concentration gave the slope and saturated value of Δ<em>f</em>_max, (Δ<em>f</em>_max)^sat<span> that are the parameters for binding property of Aβ to lipid membranes. Therefore, the Aβ-binding property on lipid membranes was classified by the slope and (Δ</span><em>f</em>_max)^sat. The plural lipid system was described as X + Y where X = L₁, L₁/L₂, and L₁/L₂/L₃. The slope and (Δ<em>f</em>_max)^sat values plotted as a function of mixing ratio of Y to X was classified on a basis of the lever principle (LP). The LP violation observed in both parameters resulted from the formation of the crevice or pothole, as Aβ-specific binding site, generated at the boundary between <em>l</em>_d and <em>l</em>_o phases. The LP violation observed only in the slope resulted from glycolipid-rich domain acting as Aβ-specific binding site. Furthermore, lipid planar membranes indicating strong LP violation favored strong fibrillogenesis. Especially, lipid planar membranes indicating the LP violation only in the slope induced lateral aggregated and spherulitic fibrillar aggregates. Thus, the classification of Aβ binding property on lipid membranes appeared to be related to the fibrillogenesis with a certain morphology.</p></div>","PeriodicalId":8760,"journal":{"name":"Biochimica et biophysica acta. Proteins and proteomics","volume":"1872 3","pages":"Article 140987"},"PeriodicalIF":3.2,"publicationDate":"2023-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138820194","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}