Biophysical chemistry最新文献

{"title":"Protein–lipid acyl chain interactions: Depth-dependent changes of segmental mobility of phospholipid in contact with bacteriorhodopsin","authors":"Yuichi Umegawa ,&nbsp;Sho Kato ,&nbsp;Sangjae Seo ,&nbsp;Wataru Shinoda ,&nbsp;Satoshi Kawatake ,&nbsp;Shigeru Matsuoka ,&nbsp;Michio Murata","doi":"10.1016/j.bpc.2024.107204","DOIUrl":"10.1016/j.bpc.2024.107204","url":null,"abstract":"<div><p>Boundary lipids surrounding membrane proteins play an essential role in protein function and structure. These protein–lipid interactions are mainly divided into electrostatic interactions between the polar amino acids of proteins and polar heads of phospholipids, and hydrophobic interactions between protein transmembrane sites and phospholipid acyl chains. Our previous report (Kawatake et al., Biochim. Biophys. Acta 1858 [2016] 2106–2115) covered a method for selectively analyzing boundary lipid interactions and showed differences in membrane protein–peripheral lipid interactions due to differences in their head group. Interactions in the hydrophobic acyl chains of phospholipids are relatively consistent among proteins, but the details of these interactions have not been elucidated. In this study, we reconstituted bacteriorhodopsin as a model protein into phospholipid membranes labeled with ²H and ¹³C for solid-state NMR measurement to investigate the depth-dependent effect of the head group structure on the lipid bilayer. The results showed that the position of the phospholipid near the carbonyl carbon was affected by the head group in terms of selectivity for protein surfaces, whereas in the deep interior of the bilayer near the leaflet interface, there was little difference between the head groups, indicating that the dependence of their interactions on the head group was much reduced.</p></div>","PeriodicalId":8979,"journal":{"name":"Biophysical chemistry","volume":"308 ","pages":"Article 107204"},"PeriodicalIF":3.8,"publicationDate":"2024-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139982314","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":"Designing surface exposed sites on Bacillus subtilis lipase A for spin-labeling and hydration studies","authors":"Afnan M. Jaufer ,&nbsp;Adam Bouhadana ,&nbsp;Amir Kharrazizadeh ,&nbsp;Mingwei Zhou ,&nbsp;Coray M. Colina ,&nbsp;Gail E. Fanucci","doi":"10.1016/j.bpc.2024.107203","DOIUrl":"https://doi.org/10.1016/j.bpc.2024.107203","url":null,"abstract":"<div><p>Spin-labeling with electron paramagnetic resonance spectroscopy (EPR) is a facile method for interrogating macromolecular flexibility, conformational changes, accessibility, and hydration. Within we present a computationally based approach for the rational selection of reporter sites in <em>Bacillus subtilis</em> lipase A (BSLA) for substitution to cysteine residues with subsequent modification with a spin-label that are expected to not significantly perturb the wild-type structure, dynamics, or enzymatic function. Experimental circular dichroism spectroscopy, Michaelis-Menten kinetic parameters and EPR spectroscopy data validate the success of this approach to computationally select reporter sites for future magnetic resonance investigations of hydration and hydration changes induced by polymer conjugation, tethering, immobilization, or amino acid substitution in BSLA. Analysis of molecular dynamic simulations of the impact of substitutions on the secondary structure agree well with experimental findings. We propose that this computationally guided approach for choosing spin-labeled EPR reporter sites, which evaluates relative surface accessibility coupled with hydrogen bonding occupancy of amino acids to the catalytic pocket via atomistic simulations, should be readily transferable to other macromolecular systems of interest including selecting sites for paramagnetic relaxation enhancement NMR studies, other spin-labeling EPR studies or any method requiring a tagging method where it is desirable to not alter enzyme stability or activity.</p></div>","PeriodicalId":8979,"journal":{"name":"Biophysical chemistry","volume":"308 ","pages":"Article 107203"},"PeriodicalIF":3.8,"publicationDate":"2024-02-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139907412","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":"Amyloids, amorphous aggregates and assemblies of peptides – Assessing aggregation","authors":"Maja Juković,&nbsp;Ivana Ratkaj,&nbsp;Daniela Kalafatovic,&nbsp;Nicholas J. Bradshaw","doi":"10.1016/j.bpc.2024.107202","DOIUrl":"10.1016/j.bpc.2024.107202","url":null,"abstract":"<div><p>Amyloid and amorphous aggregates represent the two major categories of aggregates associated with diseases, and although exhibiting distinct features, researchers often treat them as equivalent, which demonstrates the need for more thorough characterization. Here, we compare amyloid and amorphous aggregates based on their biochemical properties, kinetics, and morphological features. To further decipher this issue, we propose the use of peptide self-assemblies as minimalistic models for understanding the aggregation process. Peptide building blocks are significantly smaller than proteins that participate in aggregation, however, they make a plausible means to bridge the gap in discerning the aggregation process at the more complex, protein level. Additionally, we explore the potential use of peptide-inspired models to research the liquid-liquid phase separation as a feasible mechanism preceding amyloid formation. Connecting these concepts can help clarify our understanding of aggregation-related disorders and potentially provide novel drug targets to impede and reverse these serious illnesses.</p></div>","PeriodicalId":8979,"journal":{"name":"Biophysical chemistry","volume":"308 ","pages":"Article 107202"},"PeriodicalIF":3.8,"publicationDate":"2024-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139877655","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":"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}