Biophysical chemistry最新文献

{"title":"The processing intermediate of human amylin, pro-amylin(1–48), has in vivo and in vitro bioactivity","authors":"Giulia Mazzini ,&nbsp;Christelle Le Foll ,&nbsp;Christina N. Boyle ,&nbsp;Michael L. Garelja ,&nbsp;Alexander Zhyvoloup ,&nbsp;Matthew E.T. Miller ,&nbsp;Debbie L. Hay ,&nbsp;Daniel P. Raleigh ,&nbsp;Thomas A. Lutz","doi":"10.1016/j.bpc.2024.107201","DOIUrl":"10.1016/j.bpc.2024.107201","url":null,"abstract":"<div><p>Amylin is released by pancreatic beta-cells in response to a meal and its major soluble mature form (37 amino acid-peptide) produces its biological effects by activating amylin receptors. Amylin is derived from larger propeptides that are processed within the synthesizing beta-cell. There are suggestions that a partially processed form, pro-amylin(1-48) is also secreted. We tested the hypothesis that pro-amylin(1-48) has biological activity and that human pro-amylin(1-48) may also form toxic pre-amyloid species. Amyloid formation, the ability to cross-seed and <em>in vitro</em> toxicity were similar between human pro-amylin(1-48) and amylin. Human pro-amylin(1-48) was active at amylin-responsive receptors, though its potency was reduced at rat, but not human amylin receptors. Pro-amylin(1-48) was able to promote anorexia by activating neurons of the area postrema, amylin’s primary site of action, indicating that amylin can tolerate significant additions at the N-terminus without losing bioactivity. Our studies help to shed light on the possible roles of pro-amylin(1-48) which may be relevant for the development of future amylin-based drugs.</p></div>","PeriodicalId":8979,"journal":{"name":"Biophysical chemistry","volume":"308 ","pages":"Article 107201"},"PeriodicalIF":3.8,"publicationDate":"2024-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0301462224000309/pdfft?md5=19430bb3ad52a874fdf9749e1d406183&pid=1-s2.0-S0301462224000309-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139828529","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Different behavior of Ferguson plot between agarose and polyacrylamide gels","authors":"Yui Tomioka ,&nbsp;Teruo Akuta ,&nbsp;Masao Tokunaga ,&nbsp;Tsutomu Arakawa","doi":"10.1016/j.bpc.2024.107200","DOIUrl":"https://doi.org/10.1016/j.bpc.2024.107200","url":null,"abstract":"<div><p>In this study, we conducted Ferguson plot analyses using both agarose and polyacrylamide gels in native electrophoresis and SDS-PAGE. The results revealed intriguing differences in the behavior of bovine serum albumin (BSA) and other model proteins. Specifically, BSA exhibited Ferguson plot slopes that were dependent on the oligomer size in agarose native gel electrophoresis, while such size-dependent behavior was not observed in native-PAGE or SDS-PAGE. These findings suggest that Ferguson plot analysis is a suitable approach when using agarose gel under the electrophoretic conditions employed in this study. Furthermore, our investigation extended to model proteins with acidic isoelectric points and larger molecular weights, namely Ferritin and caseinolytic peptidase B (ClpB). Notably, these proteins displayed distinct Ferguson plot slopes when subjected to agarose gel electrophoresis. Intriguingly, when polyacrylamide gel was employed, ClpB exhibited multiple bands, each with its unique Ferguson plot slope, deviating from the expected behavior based on molecular size. This divergence in Ferguson plot characteristics between agarose and polyacrylamide gels points to an interesting and complex interplay between protein properties and gel electrophoresis conditions.</p></div>","PeriodicalId":8979,"journal":{"name":"Biophysical chemistry","volume":"307 ","pages":"Article 107200"},"PeriodicalIF":3.8,"publicationDate":"2024-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139748881","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}

{"title":"Studies on the binding of wedelolactone to human serum albumin with multi-spectroscopic analysis, molecular docking and molecular dynamic simulation","authors":"Yali Liu,&nbsp;Zhen Yuan,&nbsp;Pan Zhao,&nbsp;Changxin Li,&nbsp;Lu Qin,&nbsp;Tianlun Zhao,&nbsp;Xiaojing Zhu,&nbsp;Shuai Feng","doi":"10.1016/j.bpc.2024.107198","DOIUrl":"https://doi.org/10.1016/j.bpc.2024.107198","url":null,"abstract":"<div><p>Wedelolactone (WEL) is a small molecule compound isolated from <em>Eclipta prostrate</em> L., which has been reported to possess various biological activities such as anti-hepatotoxicity, anti-hypertension, anti-tumour, anti-phospholipase A2 and detoxification activity against snake venom. In the present study, we investigated the interaction of WEL with human serum albumin (HSA) using simultaneous fluorescence, UV–visible spectroscopy, 3D fluorescence spectroscopy, Fourier transform infrared spectroscopy (FTIR), molecular docking technique and molecular dynamics simulation. We found that the interaction between HSA and WEL can exhibit a static fluorescence burst mechanism, and the binding process is essentially spontaneous, with the main forces manifested as hydrogen bonding, van der Waals force and electrostatic interactions. Competitive binding and molecular docking studies showed that WEL preferentially bound to HSA in substructural region IIA (site I); molecular dynamics simulations showed that HSA interacted with WEL to form a stable complex, which also induced conformational changes in HSA. The study of the interaction between WEL and HSA can provide a reference for a more in-depth study of the pharmacodynamic mechanism of WEL and its further development and utilisation.</p></div>","PeriodicalId":8979,"journal":{"name":"Biophysical chemistry","volume":"307 ","pages":"Article 107198"},"PeriodicalIF":3.8,"publicationDate":"2024-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139738182","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}

{"title":"Dependence of cell's membrane potential on extracellular voltage observed in Chara globularis","authors":"Manohara Mahadeva,&nbsp;Sebastian Niestępski,&nbsp;Magdalena Kowacz","doi":"10.1016/j.bpc.2024.107199","DOIUrl":"https://doi.org/10.1016/j.bpc.2024.107199","url":null,"abstract":"<div><p>The membrane potential (V_m) of a cell results from the selective movement of ions across the cell membrane. Recent studies have revealed the presence of a gradient of voltage within a few nanometers adjacent to erythrocytes. Very notably this voltage is modified in response to changes in cell's membrane potential thus effectively extending the potential beyond the membrane and into the solution. In this study, using the microelectrode technique, we provide experimental evidence for the existence of a gradient of negative extracellular voltage (V_z) in a wide zone close to the cell wall of algal cells, extending over several micrometers. Modulating the ionic concentration of the extracellular solution with CO₂ alters the extracellular voltage and causes an immediate change in V_m. Elevated extracellular CO₂ levels depolarize the cell and hyperpolarize the zone of extracellular voltage (ZEV) by the same magnitude. This observation strongly suggests a coupling effect between V_z and V_m. An increase in the level of intracellular CO₂ (dark respiration) leads to hyperpolarization of the cell without any immediate effect on the extracellular voltage. Therefore, the metabolic activity of a cell can proceed without inducing changes in V_z. Conversely, V_z can be modified by external stimulation without metabolic input from the cell. The evolution of the ZEV, particularly around spines and wounded cells, where ion exchange is enhanced, suggests that the formation of the ZEV may be attributed to the exchange of ions across the cell wall and cell membrane. By comparing the changes in V_m in response to external stimuli, as measured by electrodes and observed using a potential-sensitive dye, we provide experimental evidence demonstrating the significance of extracellular voltage in determining the cell's membrane potential. This may have implications for our understanding of cell membrane potential generation beyond the activities of ion channels.</p></div>","PeriodicalId":8979,"journal":{"name":"Biophysical chemistry","volume":"307 ","pages":"Article 107199"},"PeriodicalIF":3.8,"publicationDate":"2024-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139709509","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}

{"title":"Alpha-synuclein phosphorylation induces amyloid conversion via enhanced electrostatic bridging: Insights from molecular modeling of the full-length protein","authors":"Pavel I. Semenyuk","doi":"10.1016/j.bpc.2024.107196","DOIUrl":"10.1016/j.bpc.2024.107196","url":null,"abstract":"<div><p>Fibril formation from alpha-synuclein is a key point in Parkinson's disease, multiple system atrophy, and other synucleinopathies. The mechanism of the amyloid-like conversion followed by the formation of pre-fibrillar soluble oligomers and fibrils is not completely clear; furthermore, it is unclear how the Parkinson's disease-related point mutations located in the pre-NAC region enhance fibrillation. In the present paper, atomistic replica exchange molecular dynamics simulations of the full-length alpha-synuclein and its two mutants, A53T and E46K, elucidated amyloid conversion intermediates. Both mutants demonstrated an enhanced tendency for the conversion but in different manners; the main intermediate conformations populated in the WT alpha-synuclein conformational ensemble disappeared due to mutations, indicating a different conversion pathway. Analysis of the preferable beta-hairpin positions and intermediate conformations seems to reflect a tendency to form a particular amyloid fibril polymorph. A strong elevation of amyloid transformation level was shown also for Ser129-phosphorylated alpha-synuclein. Altered intermediate conformations, the most preferable beta-hairpin positions in the NAC region, and prevalent salt bridges propose the formation of so-called polymorph 2 or even a novel type of fibrils. A better understanding of the detailed mechanism of the amyloid conversion sheds light on the effect of Lewy body-related phosphorylation and might help in the development of new therapeutics for synucleinopathies.</p></div>","PeriodicalId":8979,"journal":{"name":"Biophysical chemistry","volume":"307 ","pages":"Article 107196"},"PeriodicalIF":3.8,"publicationDate":"2024-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139711365","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}

{"title":"Decoding the dynamics of BCL9 triazole stapled peptide","authors":"Vikram Gaikwad,&nbsp;Asha Rani Choudhury,&nbsp;Rajarshi Chakrabarti","doi":"10.1016/j.bpc.2024.107197","DOIUrl":"https://doi.org/10.1016/j.bpc.2024.107197","url":null,"abstract":"<div><p>BCL9 is a key protein in Wnt signaling pathway. It acts as a transcriptional co-activator to β-catenin, and dysregulation in this pathway leads to tumor growth. Inhibiting such a protein-protein interaction is considered as a therapeutic challenge. The interaction between β-catenin and BCL9 is facilitated by a 23-residue helical domain from BCL9 and a hydrophobic groove of β-catenin. To prevent this interaction, a peptide that mimics the alpha-helical domain of BCL9 can be designed. Stapling is considered a successful strategy in the pursuit of designing such peptides in which amino acids side are stitched together using chemical moieties. Among the various types of cross-linkers, triazole is the most rapid and effective one synthesized via click reaction. However, the underlying interactions behind maintaining the secondary structure of stapled peptides remain less explored. In the current work, we employed the molecular dynamics simulation to study the conformational behavior of the experimentally synthesized single and double triazole stapled BCL9 peptide. Upon the addition of a triazole staple, there is a significant reduction in the conformational space of BCL9. The helical character of the stapled peptide increases with an increase in separation between the triazole cross-linkers. Also, we encompassed the Replica Exchange with Solute Tempering (REST2) simulation to validate the high-temperature response of the stapled peptide. From REST2, the PCA and t-SNE show the reduction in distinct cluster formation on the addition of triazole staple. Our study infers further development of these triazole-stapled BCL9 peptides into effective inhibitors to target the interaction between β-catenin and BCL9.</p></div>","PeriodicalId":8979,"journal":{"name":"Biophysical chemistry","volume":"307 ","pages":"Article 107197"},"PeriodicalIF":3.8,"publicationDate":"2024-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139709421","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}

{"title":"Analyzing of L-tryptophan thermodynamics and its solubility in aqueous acetonitrile blends at diverse temperatures","authors":"Avishek Saha ,&nbsp;Sourav Ghosh ,&nbsp;Sintu Ganai ,&nbsp;Puspal Mukherjee ,&nbsp;Kalachand Mahali ,&nbsp;Bidyut Saha ,&nbsp;A.M.A. Henaish ,&nbsp;Partha Sarathi Guin ,&nbsp;Perwez Alam ,&nbsp;Sanjay Roy","doi":"10.1016/j.bpc.2024.107195","DOIUrl":"https://doi.org/10.1016/j.bpc.2024.107195","url":null,"abstract":"<div><p>This paper delves into an investigation of the solubility characteristics of L-tryptophan within binary solvent systems containing aqueous acetonitrile. The primary emphasis of the study revolves around assessments based on mole fractions. The study utilizes these solubility values to assess thermodynamic constraints, including solution entropies and solution transfer free energetics. The calculated thermodynamic energies are correlated with interaction parameters, including Gibbs free energies and entropies, pertaining to the transfer of L-tryptophanfrom water to binary solvent blends of acetonitrile and water. Mathematical expressions are utilized to determine the transfer Gibbs free energies for chemical interactions, and the consequent entropies are clarified within the framework of solvent-solvent interactions. To expound upon the stability of L-tryptophan within the water-acetonitrile mixed system, we investigate the energetic aspects related to the transfer of chemicals Gibbs free energies. Additionally, standard temperature (298.15 K) is employed to calculate various related physicochemical parameters of solute/solvent.</p></div>","PeriodicalId":8979,"journal":{"name":"Biophysical chemistry","volume":"307 ","pages":"Article 107195"},"PeriodicalIF":3.8,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139694644","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}

{"title":"Identification of determinants of lipid and ion transport in TMEM16/anoctamin proteins through a Bayesian statistical analysis","authors":"Oscar Moran ,&nbsp;Paolo Tammaro","doi":"10.1016/j.bpc.2024.107194","DOIUrl":"10.1016/j.bpc.2024.107194","url":null,"abstract":"<div><p>The TMEM16/Anoctamin protein family (TMEM16x) is composed of members with different functions; some members form Ca²⁺-activated chloride channels, while others are lipid scramblases or combine the two functions. TMEM16x proteins are typically activated in response to agonist-induced rises of intracellular Ca²⁺; thus, they couple Ca²⁺-signalling with cell electrical activity or plasmalemmal lipid homeostasis. The structural domains underlying these functions are not fully defined. We used a Naïve Bayes classifier to gain insights into these domains. The method enabled identification of regions involved in either ion or lipid transport, and suggested domains for possible pharmacological exploitation. The method allowed the prediction of the transport property of any given TMEM16x. We envisage this strategy could be exploited to illuminate the structure-function relationship of any protein family composed of members playing different molecular roles.</p></div>","PeriodicalId":8979,"journal":{"name":"Biophysical chemistry","volume":"308 ","pages":"Article 107194"},"PeriodicalIF":3.8,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0301462224000231/pdfft?md5=c48c3243a527892c1b4f94b52bc21d00&pid=1-s2.0-S0301462224000231-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139818955","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Analyzing the interaction of Helicobacter pylori GAPDH with host molecules and hemin: Inhibition of hemin binding","authors":"Ane Anil kumar,&nbsp;Priyadharshini T,&nbsp;Preethi Ragunathan,&nbsp;Karthe Ponnuraj","doi":"10.1016/j.bpc.2024.107193","DOIUrl":"https://doi.org/10.1016/j.bpc.2024.107193","url":null,"abstract":"<div><p><span><span>Glyceraldehyde 3-phosphate dehydrogenase<span><span> (GAPDH) is a moonlighting enzyme. Apart from its primary role in the glycolytic pathway, in many bacterial species it is found in the extracellular milieu and also on the bacterial surface. Positioning on the bacterial surface allows the GAPDH molecule to interact with many host molecules such as plasminogen, </span>fibrinogen, </span></span>fibronectin<span>, laminin and mucin </span></span><em>etc.</em><span> This facilitates the bacterial colonization of the host. </span><span><em>Helicobacter pylori</em></span> is a major human pathogen that causes a number of gastrointestinal infections and is the main cause of gastric cancer. The binding analysis of <em>H. pylori</em> GAPDH (<em>Hp</em>GAPDH) with host molecules has not been carried out. Hence, we studied the interaction of <em>Hp</em><span><span><span>GAPDH with holo-transferrin, lactoferrin, haemoglobin, fibrinogen, fibronectin, </span>catalase<span>, plasminogen and mucin using biolayer interferometry. Highest and lowest binding </span></span>affinity was observed with lactoferrin (4.83 </span><em>±</em> 0.70 × 10⁻⁹ M) and holo-transferrin (4.27 <em>±</em> 2.39 × 10⁻⁵ M). Previous studies established GAPDH as a heme chaperone involved in intracellular heme trafficking and delivery to downstream target proteins. Therefore, to get insights into heme binding, the interaction between <em>Hp</em><span>GAPDH and hemin was analyzed. Hemin binds to </span><em>Hp</em>GAPDH with an affinity of 2.10 μM while the hemin bound <em>Hp</em>GAPDH does not exhibit activity. This suggests that hemin most likely binds at the active site of <em>Hp</em>GAPDH, prohibiting substrate binding. Blind docking of hemin with <em>Hp</em><span>GAPDH also supports positioning of hemin at the active site. Metal ions were found to inhibit the activity of </span><em>Hp</em>GAPDH, suggesting that it also possibly occupies the substrate binding site. Furthermore, with metal-bound <em>Hp</em>GAPDH, hemin binding was not observed, suggesting metal ions act as an inhibitor of hemin binding. Since GAPDH has been identified as a heme chaperone, it will be interesting to analyse the biological consequences of inhibition of heme binding to GAPDH by metal ions.</p></div>","PeriodicalId":8979,"journal":{"name":"Biophysical chemistry","volume":"307 ","pages":"Article 107193"},"PeriodicalIF":3.8,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139682372","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}

{"title":"Structural and mechanical behavior of type-I collagen fibrils in presence of induced electrostatic interactions through ionic liquids","authors":"Kuntala Banerjee ,&nbsp;K. Rasheeda ,&nbsp;Aafiya Tarannum ,&nbsp;N. Nishad Fathima","doi":"10.1016/j.bpc.2024.107192","DOIUrl":"10.1016/j.bpc.2024.107192","url":null,"abstract":"<div><p>Tuning the self-assembly of collagen has broad applications in the biomedical field owing to their desired biological performance as collagenous materials with tunable functionalities can further determine cellular responses. In this work, an attempt has been made to tune the self-assembly of collagen using ionic liquids, viz., imidazolium chloride (IC) and choline dihydrogen phosphate (CDHP) at its physiological pH, followed by probing assembled systems using various characterization methods. Turbidity measurements of fibrillar networks were performed to ascertain the rate of fibril formation in addition of imidazolium chloride and choline dihydrogen phosphate to collagen at physiological pH. Morphological changes were examined using Scanning Electron Microscope (SEM), binding affinities were measured by Microscale Thermophoresis (MST), in addition to, changes in the shear viscosity, mechanical strength of collagen fibrils when interacted with imidazolium and choline based ILs were carried out using rotational rheometer and Quartz Crystal Microbalance (QCM) measurements. Experimental result depicts that CDHP imparts better crosslinking as well as mechanical strength compare to IC, which is already known for destabilizing the triple helix structure is inhibiting the fibril formation. This self-assembled, ionic-liquid treated collagen-fibrillar system would accelerate various force modulated fibrillar network study, for mimicking the ECM and tissue engineering application.</p></div>","PeriodicalId":8979,"journal":{"name":"Biophysical chemistry","volume":"307 ","pages":"Article 107192"},"PeriodicalIF":3.8,"publicationDate":"2024-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139711366","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}