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Development of novel indicators and molecular systems for calcium sensing through protein engineering 利用蛋白质工程开发新的钙传感指标和分子系统。
IF 6.9 2区 生物学
Current Opinion in Chemical Biology Pub Date : 2025-02-01 DOI: 10.1016/j.cbpa.2024.102547
Alicia Climent-Catala, Mateo I. Sanchez
{"title":"Development of novel indicators and molecular systems for calcium sensing through protein engineering","authors":"Alicia Climent-Catala,&nbsp;Mateo I. Sanchez","doi":"10.1016/j.cbpa.2024.102547","DOIUrl":"10.1016/j.cbpa.2024.102547","url":null,"abstract":"<div><div>Intracellular calcium (Ca<sup>2+</sup>) is involved in a plethora of cell signalling processes and physiological functions. Increases in Ca<sup>2+</sup> concentration are <em>bona fide</em> biomarkers of neuronal activity, reflecting the spike count, timing, frequency, and the intensity of synaptic input. The development of genetically encoded calcium indicators (GECIs) was a significant advancement in modern neuroscience that enabled real-time visualisation of neuronal activity at single-cell resolution. These indicators leverage the conformational changes induced by calcium-binding proteins, such as calmodulin (CaM) or troponin C (TnC). Harnessing protein engineering approaches such as directed evolution yielded new GECIs with enhanced sensitivity, kinetics, and brightness. Notably, the development of calcium-based integrators, such as scFLARE (single-chain fast light- and activity-regulated expression), convert transient raises in cytosolic Ca<sup>2+</sup> into a transcriptional readout rather than an optical signal. This review summarises the latest efforts in protein engineering to develop new indicators and molecular systems to sense changes in Ca<sup>2+</sup> concentrations.</div></div>","PeriodicalId":291,"journal":{"name":"Current Opinion in Chemical Biology","volume":"84 ","pages":"Article 102547"},"PeriodicalIF":6.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142783566","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Synthetic peptide scaffolds as ion channels and molecular carriers 合成多肽支架作为离子通道和分子载体。
IF 6.9 2区 生物学
Current Opinion in Chemical Biology Pub Date : 2025-02-01 DOI: 10.1016/j.cbpa.2024.102563
Manuel Pérez-Pérez, Alberto Fuertes, Javier Montenegro
{"title":"Synthetic peptide scaffolds as ion channels and molecular carriers","authors":"Manuel Pérez-Pérez,&nbsp;Alberto Fuertes,&nbsp;Javier Montenegro","doi":"10.1016/j.cbpa.2024.102563","DOIUrl":"10.1016/j.cbpa.2024.102563","url":null,"abstract":"<div><div>Transmembrane ion exchange controls biological functions and is essential for life. Over the years, a great variety of nature-inspired artificial ion channels and carriers have been synthesized to control and promote ion exchange across biological membranes. In this context, peptides emerged as ideal scaffolds for synthetic ion channels due to their biocompatibility, accessibility and chemical versatility. Peptides have already shown their potential for the construction of a range of synthetic ion transporters either alone or in combination with other molecular scaffolds. Among the great diversity of peptide-based ion transporters, we can find key examples of single-molecule and supramolecular transmembrane ion channels and ionophores. Peptide scaffolds have also found great potential for the transmembrane delivery of biomolecular cargos such as nucleic acids and proteins. This review covers some of the most relevant advances in the peptide-based ion transport field from the last few years.</div></div>","PeriodicalId":291,"journal":{"name":"Current Opinion in Chemical Biology","volume":"84 ","pages":"Article 102563"},"PeriodicalIF":6.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142942112","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Foldamer-mediated transport across phospholipid bilayers 折叠体介导的磷脂双层转运
IF 6.9 2区 生物学
Current Opinion in Chemical Biology Pub Date : 2024-11-30 DOI: 10.1016/j.cbpa.2024.102549
Iqra Zubair , Luis Martínez-Crespo , Simon J. Webb
{"title":"Foldamer-mediated transport across phospholipid bilayers","authors":"Iqra Zubair ,&nbsp;Luis Martínez-Crespo ,&nbsp;Simon J. Webb","doi":"10.1016/j.cbpa.2024.102549","DOIUrl":"10.1016/j.cbpa.2024.102549","url":null,"abstract":"<div><div>Crucial physiological processes, like neural communication and muscle contraction, are mediated by protein channels in cell membranes. These natural channels typically have a central hydrophilic pore with tightly defined dimensions, which can be opened or closed (‘gated’) by external stimuli. Mimicking natural ion channels using synthetic molecules is a long-standing goal in artificial channel research. Although current synthetic channels have not yet achieved the same combination of high activity, high selectivity, and gating as natural channels, foldamers offer a new approach. Foldamers are unnatural oligomers that fold into defined three-dimensional shapes, similar to the way that natural polypeptides fold into secondary structures. With defined shapes and often multi-nanometre dimensions, foldamers have become valuable tools to mimic the behaviour of natural proteins in membranes. This review highlights selected recent examples of foldamer channels, examples that indicate how foldamer architectures may lead to controllable channels with high activity and selectivity.</div></div>","PeriodicalId":291,"journal":{"name":"Current Opinion in Chemical Biology","volume":"84 ","pages":"Article 102549"},"PeriodicalIF":6.9,"publicationDate":"2024-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142746714","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Discovering microbiota functions via chemical probe incorporation for targeted sequencing 通过化学探针结合发现微生物群功能，用于靶向测序
IF 6.9 2区 生物学
Current Opinion in Chemical Biology Pub Date : 2024-11-30 DOI: 10.1016/j.cbpa.2024.102551
Natalie Falco , Matthew E. Griffin
{"title":"Discovering microbiota functions via chemical probe incorporation for targeted sequencing","authors":"Natalie Falco ,&nbsp;Matthew E. Griffin","doi":"10.1016/j.cbpa.2024.102551","DOIUrl":"10.1016/j.cbpa.2024.102551","url":null,"abstract":"<div><div>Our microbiota plays crucial roles in immune development and homeostasis and has been implicated in virtually all major diseases of the 21st century. Nevertheless, our understanding of the exact microbial functions that underlie these correlations remains extremely limited, due in large part to the difficulty of profiling cellular activities within non-model organisms and complex communities. Over the past decade, new flow cytometric approaches have been developed to distinguish specific microbial populations based on their interactions with metabolite analogs, modified biomolecules, and reactive compounds. By selecting and separating active microbes via fluorescence-activated cell sorting, PRobe INcorporation for Targeted sequencing (PRINT-seq) has inspired innovative approaches to identify and characterize functional members of our microbiota. Here, we provide a broad overview of this evolving technology and summarize how this method has been recently employed as a diagnostic fingerprint for diverse microbial activities.</div></div>","PeriodicalId":291,"journal":{"name":"Current Opinion in Chemical Biology","volume":"84 ","pages":"Article 102551"},"PeriodicalIF":6.9,"publicationDate":"2024-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142746713","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Forty sites of TRP channel regulation 40个TRP通道调控位点
IF 6.9 2区 生物学
Current Opinion in Chemical Biology Pub Date : 2024-11-30 DOI: 10.1016/j.cbpa.2024.102550
Irina A. Talyzina, Kirill D. Nadezhdin, Alexander I. Sobolevsky
{"title":"Forty sites of TRP channel regulation","authors":"Irina A. Talyzina,&nbsp;Kirill D. Nadezhdin,&nbsp;Alexander I. Sobolevsky","doi":"10.1016/j.cbpa.2024.102550","DOIUrl":"10.1016/j.cbpa.2024.102550","url":null,"abstract":"<div><div>Transient receptor potential (TRP) channels are polymodal molecular sensors that integrate chemical, thermal, mechanical and electrical stimuli and convert them into ionic currents that regulate senses of taste, smell, vision, hearing, touch and contribute to perception of temperature and pain. TRP channels are implicated in the pathogenesis of numerous human diseases, including cancers, and represent one of the most ardently pursued drug targets. Recent advances in structural biology, particularly associated with the cryo-EM “resolution revolution”, yielded numerous TRP channel structures in complex with ligands that might have therapeutic potential. In this review, we describe the recent progress in TRP channel structural biology, focusing on the description of identified binding sites for small molecules, their relationship to membrane lipids, and interaction of TRP channels with other proteins. The characterized binding sites and interfaces create a diversity of druggable targets and provide a roadmap to aid in the design of new molecules for tuning TRP channel function in disease conditions.</div></div>","PeriodicalId":291,"journal":{"name":"Current Opinion in Chemical Biology","volume":"84 ","pages":"Article 102550"},"PeriodicalIF":6.9,"publicationDate":"2024-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142746712","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Corrigendum to “Drug discovery targeting Nav1.8: Structural insights and therapeutic potential” [Curr Opin Chem Biol 83 (2024) 102538] 针对 Nav1.8 的药物发现：结构见解和治疗潜力》[Curr Opin Chem Biol 83 (2024) 102538] 更正
IF 6.9 2区 生物学
Current Opinion in Chemical Biology Pub Date : 2024-11-25 DOI: 10.1016/j.cbpa.2024.102546
Huan Wang , Jian Huang , Jie Zang , Xueqin Jin , Nieng Yan
{"title":"Corrigendum to “Drug discovery targeting Nav1.8: Structural insights and therapeutic potential” [Curr Opin Chem Biol 83 (2024) 102538]","authors":"Huan Wang ,&nbsp;Jian Huang ,&nbsp;Jie Zang ,&nbsp;Xueqin Jin ,&nbsp;Nieng Yan","doi":"10.1016/j.cbpa.2024.102546","DOIUrl":"10.1016/j.cbpa.2024.102546","url":null,"abstract":"","PeriodicalId":291,"journal":{"name":"Current Opinion in Chemical Biology","volume":"84 ","pages":"Article 102546"},"PeriodicalIF":6.9,"publicationDate":"2024-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142700374","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Engineered metallobiocatalysts for energy–relevant reactions 用于能源相关反应的工程金属生物催化剂
IF 6.9 2区 生物学
Current Opinion in Chemical Biology Pub Date : 2024-11-25 DOI: 10.1016/j.cbpa.2024.102545
Ryan M. Kosko , Kaye L. Kuphal , Alison A. Salamatian , Kara L. Bren
{"title":"Engineered metallobiocatalysts for energy–relevant reactions","authors":"Ryan M. Kosko ,&nbsp;Kaye L. Kuphal ,&nbsp;Alison A. Salamatian ,&nbsp;Kara L. Bren","doi":"10.1016/j.cbpa.2024.102545","DOIUrl":"10.1016/j.cbpa.2024.102545","url":null,"abstract":"<div><div>Engineering metallobiocatalysts is a promising approach to addressing challenges in energy-relevant electrocatalysis and photocatalysis. The design freedom provided by semisynthetic and fully synthetic approaches to catalyst design allows researchers to demonstrate how structural modifications can improve selectivity and activity of biocatalysts. Furthermore, the provision of a superstructure in many metallobiocatalysts facilitates active-site microenvironment engineering. Recurring themes include the role of the biomolecular scaffold in enhancing reactivity in water and catalyst robustness, the impact of the outer sphere on reactivity, and the importance of tuning system components in full system optimization. In this perspective, recent strategies to design and modify novel biocatalysts, understand proton and electron transfer mechanisms, and tune system activity by modifying catalysts and system conditions are highlighted within the field of energy-related catalysis. Opportunities in this field include developing robust structure–function relationships to support approaches to engineering second-sphere interactions and identifying ways to enhance biocatalyst activity over time.</div></div>","PeriodicalId":291,"journal":{"name":"Current Opinion in Chemical Biology","volume":"84 ","pages":"Article 102545"},"PeriodicalIF":6.9,"publicationDate":"2024-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142700373","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Synthetic ion channels in biomembranes 生物膜中的合成离子通道。
IF 6.9 2区 生物学
Current Opinion in Chemical Biology Pub Date : 2024-11-20 DOI: 10.1016/j.cbpa.2024.102544
Ai Kohata , Kazushi Kinbara
{"title":"Synthetic ion channels in biomembranes","authors":"Ai Kohata ,&nbsp;Kazushi Kinbara","doi":"10.1016/j.cbpa.2024.102544","DOIUrl":"10.1016/j.cbpa.2024.102544","url":null,"abstract":"<div><div>Ion transport across cell membranes is crucial in maintaining ion homeostasis in cells. Synthetic molecules that can mimic the functions of natural ion channel proteins would possess great potential as therapeutic agents by promoting apoptosis or interfering with autophagic processes through perturbing the intracellular pH or inducing oxidative and osmotic stresses. However, little is known about the underlying mechanisms in terms of direct correlation between ion transport and biological functions. This review summarizes recent progress in the area of synthetic transmembrane ion transport systems, focusing on the channel type, with an emphasis on their bioapplications as anticancer agents.</div></div>","PeriodicalId":291,"journal":{"name":"Current Opinion in Chemical Biology","volume":"84 ","pages":"Article 102544"},"PeriodicalIF":6.9,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142685693","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Transferring enzyme features to molecular CO2 reduction catalysts 将酶的特性转化为分子二氧化碳还原催化剂。
IF 6.9 2区 生物学
Current Opinion in Chemical Biology Pub Date : 2024-11-15 DOI: 10.1016/j.cbpa.2024.102540
Matthias Huber, Corinna R. Hess
{"title":"Transferring enzyme features to molecular CO2 reduction catalysts","authors":"Matthias Huber,&nbsp;Corinna R. Hess","doi":"10.1016/j.cbpa.2024.102540","DOIUrl":"10.1016/j.cbpa.2024.102540","url":null,"abstract":"<div><div>Carbon monoxide dehydrogenases and formate dehydrogenases efficiently catalyze the reduction of CO<sub>2</sub>. In both enzymes, CO<sub>2</sub> activation at the metal active site is assisted by proximate amino acids and Fe–S-clusters. Functional features of the enzyme are mimicked in molecular catalysts by redox-active ligands, acidic and charged groups in the ligand periphery, and binuclear scaffolds. These components have all improved the catalytic performance of synthetic systems. Recent studies impart a deeper understanding of the individual contributions of the various functionalities to reactivity and of their combined effects. New catalyst platforms reveal alternate pathways for CO<sub>2</sub> reduction, unique intermediates, and strategies for switching selectivity. Design of a wider array of complexes that combine different functional elements is encouraged to further optimize catalysts for CO<sub>2</sub> reduction, especially for product formation beyond CO. More diverse bimetallic catalysts are needed to better exploit metal–metal interactions for CO<sub>2</sub> conversion.</div></div>","PeriodicalId":291,"journal":{"name":"Current Opinion in Chemical Biology","volume":"83 ","pages":"Article 102540"},"PeriodicalIF":6.9,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142643601","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Synthetic transporters for oxoanions 氧阴离子合成转运体。
IF 6.9 2区 生物学
Current Opinion in Chemical Biology Pub Date : 2024-11-14 DOI: 10.1016/j.cbpa.2024.102542
Karolis Norvaisa, Aaron Torres-Huerta, Hennie Valkenier
{"title":"Synthetic transporters for oxoanions","authors":"Karolis Norvaisa,&nbsp;Aaron Torres-Huerta,&nbsp;Hennie Valkenier","doi":"10.1016/j.cbpa.2024.102542","DOIUrl":"10.1016/j.cbpa.2024.102542","url":null,"abstract":"<div><div>This brief review highlights recent advances in the transport of oxoanions using synthetic carriers, focusing on both progress and ongoing challenges in the field. The difficulty of transporting these oxoanions increases with their hydration enthalpies, with less hydrated nitrate and perchlorate being relatively easy to transport. Recent progress has focused on the transport of moderately hydrated anions such as bicarbonate and carboxylates, where studies are influenced by the free diffusion of neutral species obtained by (de)protonation equilibria. Despite significant innovations in the design of synthetic carriers, the transport of the highly hydrated oxoanions sulfate and phosphate remains a major challenge. Progress on sulfate transport has stalled, while the first example of phosphate transport was reported only last year.</div></div>","PeriodicalId":291,"journal":{"name":"Current Opinion in Chemical Biology","volume":"83 ","pages":"Article 102542"},"PeriodicalIF":6.9,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142610819","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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