Biophysical chemistry最新文献

{"title":"Glycerol-slaved 1H-1H NMR cross-relaxation in quasi-native lysozyme","authors":"Kirthi Joshi,&nbsp;Abani K. Bhuyan","doi":"10.1016/j.bpc.2024.107286","DOIUrl":"10.1016/j.bpc.2024.107286","url":null,"abstract":"<div><p>¹H-¹H nuclear cross-relaxation experiments have been carried out with lysozyme in variable glycerol viscosity to study intramolecular motion, self-diffusion, and isotropic rigid-body rotational tumbling at 298 K, pH 3.8. Dynamics of intramolecular ¹H-¹H cross-relaxation rates, the increase in internuclear spatial distances, and lateral and rotational diffusion coefficients all show fractional viscosity dependence with a power law exponent <em>κ</em> in the 0.17–0.83 range. The diffusion coefficient of glycerol <em>D</em>_s with the bulk viscosity itself is non-Stokesian, having a fractional viscosity dependence on the medium viscosity (<em>D</em>_s ∼ <em>η</em>^-<em>κ</em>, <em>κ</em> ≈ 0.71). The concurrence and close similarity of the fractional viscosity dependence of glycerol diffusion on the one hand, and diffusion and intramolecular cross-relaxation rates of the protein on the other lead to infer that relaxation of glycerol slaves protein relaxations. Glycerol-transformed native lysozyme to a quasi-native state does not affect the conclusion that both global and internal fluctuations are slaved to glycerol relaxation.</p></div>","PeriodicalId":8979,"journal":{"name":"Biophysical chemistry","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141533541","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":"Nanoscale intracellular ultrastructures affected by osmotic pressure using small-angle X-ray scattering","authors":"Masaru Nakada ,&nbsp;Junko Kanda ,&nbsp;Hironobu Uchiyama ,&nbsp;Kazuaki Matsumura","doi":"10.1016/j.bpc.2024.107287","DOIUrl":"10.1016/j.bpc.2024.107287","url":null,"abstract":"<div><p>Although intracellular ultrastructures have typically been studied using microscopic techniques, it is difficult to observe ultrastructures at the submicron scale of living cells due to spatial resolution (fluorescence microscopy) or high vacuum environment (electron microscopy). We investigate the nanometer scale intracellular ultrastructures of living CHO cells in various osmolality using small-angle X-ray scattering (SAXS), and especially the structures of ribosomes, DNA double helix, and plasma membranes <em>in-cell</em> environment are observed. Ribosomes expand and contract in response to osmotic pressure, and the inter-ribosomal correlation occurs under isotonic and hyperosmolality. The DNA double helix is not dependent on the osmotic pressure. Under high osmotic pressure, the plasma membrane folds into form a multilamellar structure with a periodic length of about 6 nm. We also study the ultrastructural changes caused by formaldehyde fixation, freezing and heating.</p></div>","PeriodicalId":8979,"journal":{"name":"Biophysical chemistry","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141562543","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":"Understanding the structural dynamics of human islet amyloid polypeptide: Advancements in and applications of ion-mobility mass spectrometry","authors":"Zijie Dai ,&nbsp;Aisha Ben-Younis ,&nbsp;Anna Vlachaki ,&nbsp;Daniel Raleigh ,&nbsp;Konstantinos Thalassinos","doi":"10.1016/j.bpc.2024.107285","DOIUrl":"10.1016/j.bpc.2024.107285","url":null,"abstract":"<div><p>Human islet amyloid polypeptide (hIAPP) forms amyloid deposits that contribute to β-cell death in pancreatic islets and are considered a hallmark of Type II diabetes Mellitus (T2DM). Evidence suggests that the early oligomers of hIAPP formed during the aggregation process are the primary pathological agent in islet amyloid induced β-cell death. The self-assembly mechanism of hIAPP, however, remains elusive, largely due to limitations in conventional biophysical techniques for probing the distribution or capturing detailed structures of the early, structurally dynamic oligomers. The advent of Ion-mobility Mass Spectrometry (IM-MS) has enabled the characterisation of hIAPP early oligomers in the gas phase, paving the way towards a deeper understanding of the oligomerisation mechanism and the correlation of structural information with the cytotoxicity of the oligomers. The sensitivity and the rapid structural characterisation provided by IM-MS also show promise in screening hIAPP inhibitors, categorising their modes of inhibition through “spectral fingerprints”. This review delves into the application of IM-MS to the dissection of the complex steps of hIAPP oligomerisation, examining the inhibitory influence of metal ions, and exploring the characterisation of hetero-oligomerisation with different hIAPP variants. We highlight the potential of IM-MS as a tool for the high-throughput screening of hIAPP inhibitors, and for providing insights into their modes of action. Finally, we discuss advances afforded by recent advancements in tandem IM-MS and the combination of gas phase spectroscopy with IM-MS, which promise to deliver a more sensitive and higher-resolution structural portrait of hIAPP oligomers. Such information may help facilitate a new era of targeted therapeutic strategies for islet amyloidosis in T2DM.</p></div>","PeriodicalId":8979,"journal":{"name":"Biophysical chemistry","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0301462224001145/pdfft?md5=866ee42ad142b7d7508377247543f8c8&pid=1-s2.0-S0301462224001145-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141465958","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":"Membrane lateral organization from potential energy disconnectivity graph","authors":"Sahithya Sridharan Iyer ,&nbsp;Anand Srivastava","doi":"10.1016/j.bpc.2024.107284","DOIUrl":"10.1016/j.bpc.2024.107284","url":null,"abstract":"<div><p>Understanding the thermodynamic and kinetic properties of biomolecules requires elucidation of their complex energy landscape. A disconnectivity graph analysis of the energy landscape provides a framework for mapping the multi-dimensional landscape onto a two-dimensional representation while preserving the key features of the energy landscape. Several studies show that the structure or shape of the disconnectity graph is directly associated with the function of protein and nucleic acid molecules. In this review, we discuss how disconnectivity analysis of the potential energy surface can be extended to lipid molecules to glean important information about membrane organization. The shape of the disconnectivity graphs can be used to predict the lateral organization of multi-component lipid bilayer. We hope that this review encourages the use of disconnectivity graphs routinely by membrane biophysicists to predict the lateral organization of lipids.</p></div>","PeriodicalId":8979,"journal":{"name":"Biophysical chemistry","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141603275","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":"Effects of an external static EF on the conformational transition of 5-HT1A receptor: A molecular dynamics simulation study","authors":"Lulu Guan ,&nbsp;Jingwang Tan ,&nbsp;Bote Qi ,&nbsp;Yukang Chen ,&nbsp;Meng Cao ,&nbsp;Qingwen Zhang ,&nbsp;Yu Zou","doi":"10.1016/j.bpc.2024.107283","DOIUrl":"10.1016/j.bpc.2024.107283","url":null,"abstract":"<div><p>The serotonin receptor subtype 1A (5-HT1AR), one of the G-protein-coupled receptor (GPCR) family, has been implicated in several neurological conditions. Understanding the activation and inactivation mechanism of 5-HT1AR at the molecular level is critical for discovering novel therapeutics in many diseases. Recently there has been a growing appreciation for the role of external electric fields (EFs) in influencing the structure and activity of biomolecules. In this study, we used molecular dynamics (MD) simulations to examine conformational features of active states of 5-HT1AR and investigate the effect of an external static EF with 0.02 V/nm applied on the active state of 5-HT1AR. Our results showed that the active state of 5-HT1AR maintained the native structure, while the EF led to structural modifications in 5-HT1AR, particularly inducing the inward movement of transmembrane helix 6 (TM6). Furthermore, it disturbed the conformational switches associated with activation in the CWxP, DRY, PIF, and NPxxY motifs, consequently predisposing an inclination towards the inactive-like conformation. We also found that the EF led to an overall increase in the dipole moment of 5-HT1AR, encompassing TM6 and pivotal amino acids. The analyses of conformational properties of TM6 showed that the changed secondary structure and decreased solvent exposure occurred upon the EF condition. The interaction of 5-HT1AR with the membrane lipid bilayer was also altered under the EF. Our findings reveal the molecular mechanism underlying the transition of 5-HT1AR conformation induced by external EFs, which offer potential novel insights into the prospect of employing structure-based EF applications for GPCRs.</p></div>","PeriodicalId":8979,"journal":{"name":"Biophysical chemistry","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141465956","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 contrasting roles of co-solvents in protein formulations and food products","authors":"Tsutomu Arakawa ,&nbsp;Yui Tomioka ,&nbsp;Teruo Akuta ,&nbsp;Kentaro Shiraki","doi":"10.1016/j.bpc.2024.107282","DOIUrl":"10.1016/j.bpc.2024.107282","url":null,"abstract":"<div><p>Protein aggregation is a major hurdle in developing biopharmaceuticals, in particular protein formulation area, but plays a pivotal role in food products. Co-solvents are used to suppress protein aggregation in pharmaceutical proteins. On the contrary, aggregation is encouraged in the process of food product making. Thus, it is expected that co-solvents play a contrasting role in biopharmaceutical formulation and food products. Here, we show several examples that utilize co-solvents, e.g., salting-out salts, sugars, polyols and divalent cations in promoting protein-protein interactions. The mechanisms of co-solvent effects on protein aggregation and solubility have been studied on aqueous protein solution and applied to develop pharmaceutical formulation based on the acquired scientific knowledge. On the contrary, co-solvents have been used in food industries based on empirical basis. Here, we will review the mechanisms of co-solvent effects on protein-protein interactions that can be applied to both pharmaceutical and food industries and hope to convey knowledge acquired through research on co-solvent interactions in aqueous protein solution and formulation to those involved in food science and provide those involved in protein solution research with the observations on aggregation behavior of food proteins.</p></div>","PeriodicalId":8979,"journal":{"name":"Biophysical chemistry","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141465957","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":"Global kinetic mechanism describing single nucleotide incorporation for RNA polymerase I reveals fast UMP incorporation","authors":"Kaila B. Fuller ,&nbsp;Ruth Q. Jacobs ,&nbsp;Zachariah I. Carter ,&nbsp;Zachary G. Cuny ,&nbsp;David A. Schneider ,&nbsp;Aaron L. Lucius","doi":"10.1016/j.bpc.2024.107281","DOIUrl":"10.1016/j.bpc.2024.107281","url":null,"abstract":"<div><p>RNA polymerase I (Pol I) is responsible for synthesizing ribosomal RNA, which is the rate limiting step in ribosome biogenesis. We have reported wide variability in the magnitude of the rate constants defining the rate limiting step in sequential nucleotide additions catalyzed by Pol I. in this study we sought to determine if base identity impacts the rate limiting step of nucleotide addition catalyzed by Pol I. To this end, we report a transient state kinetic interrogation of AMP, CMP, GMP, and UMP incorporations catalyzed by Pol I. We found that Pol I uses one kinetic mechanism to incorporate all nucleotides. However, we found that UMP incorporation is faster than AMP, CMP, and GMP additions. Further, we found that endonucleolytic removal of a dimer from the 3′ end was fastest when the 3′ terminal base is a UMP. It has been previously shown that both downstream and upstream template sequence identity impacts the kinetics of nucleotide addition. The results reported here show that the incoming base identity also impacts the magnitude of the observed rate limiting step.</p></div>","PeriodicalId":8979,"journal":{"name":"Biophysical chemistry","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141404966","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":"Flexible RNA aptamers as inhibitors of Bacillus anthracis ribosomal protein S8: Insights from molecular dynamics simulations","authors":"Pradeep Pant","doi":"10.1016/j.bpc.2024.107273","DOIUrl":"10.1016/j.bpc.2024.107273","url":null,"abstract":"<div><p><em>Bacillus anthracis</em>, the causative agent of anthrax, poses a substantial threat to public health and national security, and is recognized as a potential bioweapon due to its capacity to form resilient spores with enduring viability. Inhalation or ingestion of even minute quantities of aerosolized spores can lead to widespread illness and fatalities, underscoring the formidable lethality of the bacterium. With an untreated mortality rate of 100%, <em>Bacillus anthracis</em> is a disconcerting candidate for bioterrorism. In response to this critical scenario, we employed state-of-the-art computational tools to conceive and characterize flexible RNA aptamer therapeutics tailored for anthrax. The foundational structure of the flexible RNA aptamers was designed by removing the C2’-C3’ in each nucleotide unit. Leveraging the crystal structure of <em>Bacillus anthracis</em> ribosomal protein S8 complexed with an RNA aptamer, we explored the structural, dynamic, and energetic aspects of the modified RNA aptamer – S8 protein complexes through extensive all-atom explicit-solvent molecular dynamics simulations (400 ns, 3 replicas each), followed by drawing comparisons to the control system. Our findings demonstrate the enhanced binding competencies of the flexible RNA aptamers to the S8 protein via better shape complementarity and improved H-bond network compared to the control RNA aptamer. This research offers valuable insights into the development of RNA aptamer therapeutics targeting <em>Bacillus anthracis</em>, paving the way for innovative strategies to mitigate the impact of this formidable pathogen.</p></div>","PeriodicalId":8979,"journal":{"name":"Biophysical chemistry","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141276615","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":"Exploring the solubility and intermolecular interactions of biologically significant amino acids l-serine and L-cysteine in binary mixtures of H2O + DMF, H2O + DMSO and H2O + ACN in temperature range from T = 288.15 K to 308.15 K","authors":"Jit Chakraborty ,&nbsp;Kalachand Mahali ,&nbsp;A.M.A. Henaish ,&nbsp;Jahangeer Ahmed ,&nbsp;Saad M. Alshehri ,&nbsp;Aslam Hossain ,&nbsp;Sanjay Roy","doi":"10.1016/j.bpc.2024.107272","DOIUrl":"10.1016/j.bpc.2024.107272","url":null,"abstract":"<div><p>In the presented work, a study on the solubility and intermolecular interactions of <span>l</span>-serine and L-cysteine was carried out in binary mixtures of H₂O + dimethylformamide (DMF), H₂O + dimethylsulfoxide (DMSO), and H₂O + acetonitrile (ACN) in the temperature range of <em>T</em> = 288.15 K to 308.15 K. <span>l</span>-serine exhibited the highest solubility in water, while L-cysteine was more soluble in water-DMF. The solvation process was assessed through standard Gibbs energy calculations, indicating the solvation stability order: water-ACN &gt; water-DMSO &gt; water-DMF for <span>l</span>-serine, and water-DMF &gt; water-DMSO &gt; water-ACN for L-cysteine. This study also explored the influence of these amino acids on solvent–solvent interactions, revealing changes in chemical entropies and self-association patterns within the binary solvent mixtures.</p></div>","PeriodicalId":8979,"journal":{"name":"Biophysical chemistry","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141199285","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":"Inside of the burst-phase intermediate of a protein folding. Hydration of hydrophobic groups","authors":"Elena I. Bolonova ,&nbsp;Tatiana N. Melnik ,&nbsp;Sergey A. Potekhin","doi":"10.1016/j.bpc.2024.107268","DOIUrl":"10.1016/j.bpc.2024.107268","url":null,"abstract":"<div><p>The thermal effect of the formation of the “burst-phase” folding intermediate has been studied using a titration calorimeter. It is shown that, unlike the total thermal effect of native structure formation, it can be both positive and negative depending on the temperature. The reasons for this paradoxical behavior are analyzed. A conclusion is drawn about the leading role of dehydration of non-polar groups in the first stage of folding.</p></div>","PeriodicalId":8979,"journal":{"name":"Biophysical chemistry","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141282953","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}