Advances in protein chemistry and structural biology最新文献

Engineering of antimicrobial peptides by surface display technologies. 表面显示技术在抗菌肽工程中的应用。

3区生物学

Advances in protein chemistry and structural biology Pub Date : 2026-01-01 Epub Date: 2025-05-12 DOI: 10.1016/bs.apcsb.2025.04.004

Sugra Yuceer, Husniye Tansel Yalcin, Sibel Kalyoncu

{"title":"Engineering of antimicrobial peptides by surface display technologies.","authors":"Sugra Yuceer, Husniye Tansel Yalcin, Sibel Kalyoncu","doi":"10.1016/bs.apcsb.2025.04.004","DOIUrl":"https://doi.org/10.1016/bs.apcsb.2025.04.004","url":null,"abstract":"The emergence of antibiotic-resistant pathogens mostly due to intensive antibiotic use greatly endangers human health. For this reason, it has become necessary to search for new drugs or alternative treatments that are effective on resistant microorganisms. This review examines antimicrobial peptides (AMPs) which are part of the first primitive defense mechanism used by both eukaryotic and prokaryotic cells against many pathogens. AMPs are usually small (up to 50 amino acids), cationic peptides which make them bind to negatively charged cell membranes of pathogens for permeabilization and destruction. AMPs can act on antibiotic-resistant pathogens such as Enterococcus faecium, methicillin-resistant Staphylococcus aureus (MRSA), and Pseudomonas aeruginosa, and they offer unique advantages due to their membrane-active antimicrobial mechanisms that reduce the likelihood of developing resistance. AMPs have high therapeutic potential due to their broad-spectrum activities, and different mechanisms of action compared to traditional antibiotics. However, their practical application is often hampered by their limited activity, host toxicity and poor stability. To overcome these limitations, natural AMP sequences can be improved by protein engineering approaches. Surface display technology is one of the leading high-throughput protein engineering strategies where primary/secondary structures of AMPs can be modified and screened for various improvements. This review focuses on the key properties of antimicrobial peptides, as well as insights on the use of in vitro surface display techniques to develop next-generation AMPs for therapeutic uses.","PeriodicalId":7376,"journal":{"name":"Advances in protein chemistry and structural biology","volume":"149 ","pages":"115-141"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146045984","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}

引用次数: 0

Mechanism of tau proteins differentially regulating the motility of different families of kinesin motors. tau蛋白差异调节不同家族运动的机制。

3区生物学

Advances in protein chemistry and structural biology Pub Date : 2026-01-01 Epub Date: 2025-11-25 DOI: 10.1016/bs.apcsb.2025.10.024

Ping Xie

{"title":"Mechanism of tau proteins differentially regulating the motility of different families of kinesin motors.","authors":"Ping Xie","doi":"10.1016/bs.apcsb.2025.10.024","DOIUrl":"https://doi.org/10.1016/bs.apcsb.2025.10.024","url":null,"abstract":"It was shown experimentally that the motility of different families of kinesin motors can be differentially regulated by microtubule-associated tau proteins. However, the underlying mechanism is unclear. To address the mechanism, here we take three kinesin motors-kinesin-1, kinesin-3 and kinesin-8-as examples to study theoretically the motility of the kinesin motor within the tau island and at the island boundary. The theoretical results show that after landing within the tau island, a kinesin-8 motor can move processively for a long time of about 80 s and for a long run length of about 1.6 µm, a kinesin-1 motor can dissociate in a short time of about 0.35 s, while a kinesin-3 motor can dissociate in a much shorter time of about 0.01 s. The kinesin-8 motors can induce the receding of the tau island with a velocity similar to a kinesin-8 stepping within the island, kinesin-1 motors can hardly induce the island receding, while kinesin-3 motors have a much lower probability to induce the island receding than kinesin-1 motors. The theoretical results explain well the available experimental data. The studies indicate that the tau island differentially regulating the motility of different kinesin motors is due mainly to different residence times of the motors with a stationary small obstacle on the front tubulin.","PeriodicalId":7376,"journal":{"name":"Advances in protein chemistry and structural biology","volume":"150 ","pages":"377-396"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147571831","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}

引用次数: 0

Antimicrobial peptides: Bridging mechanistic understanding and novel applications. 抗菌肽：桥接机制的理解和新的应用。

3区生物学

Advances in protein chemistry and structural biology Pub Date : 2026-01-01 Epub Date: 2025-08-30 DOI: 10.1016/bs.apcsb.2025.08.004

Wanzhen Dai, Bee K Tan, Jiamiao Hu

引用次数: 0

Cytoskeletal proteins regulates Tau protein in Alzheimer's disease. 细胞骨架蛋白在阿尔茨海默病中调节Tau蛋白。

3区生物学

Advances in protein chemistry and structural biology Pub Date : 2026-01-01 Epub Date: 2025-11-14 DOI: 10.1016/bs.apcsb.2025.10.029

Subashchandrabose Chinnathambi, Anusree Adityan

{"title":"Cytoskeletal proteins regulates Tau protein in Alzheimer's disease.","authors":"Subashchandrabose Chinnathambi, Anusree Adityan","doi":"10.1016/bs.apcsb.2025.10.029","DOIUrl":"https://doi.org/10.1016/bs.apcsb.2025.10.029","url":null,"abstract":"Cytoskeletal proteins, particularly microtubules and actin, play critical roles in maintaining neuronal structure, transport, and function. In Alzheimer's disease (AD), the Tau protein, which normally stabilizes microtubules, becomes hyperphosphorylated and forms neurofibrillary tangles, leading to Tauopathies. This pathological change disrupts microtubule dynamics, axonal transport, and overall neuronal integrity. The cytoskeletal proteins like actin, tubulin, MAPs, ankyrin, gelsolin, vimentin, drebrin, septins, cofilin, spectrin, intermediate filaments and Tau role and function in Alzheimer's disease. Cross-talk between microtubules and actin further exacerbates Tau pathology, contributing to synaptic dysfunction, oxidative stress, and neuronal degeneration and dysregulation accelerates neurodegenerative processes, and Tauopathies. Tau pathology impairs synaptic plasticity by disrupting both actin and microtubule cytoskeletons, leading to dendritic spine loss, synaptic failure, and memory impairment. Compounds that prevent tau hyperphosphorylation or promote its dephosphorylation (e.g., GSK-3β inhibitors) may help stabilize microtubules. Cytoskeletal dysfunction is associated with oxidative stress. Compounds that reduce oxidative stress could protect the cytoskeleton from further damage. Since inflammation exacerbates tau pathology and cytoskeletal breakdown, targeting neuroinflammation may have protective effects on cytoskeletal integrity.","PeriodicalId":7376,"journal":{"name":"Advances in protein chemistry and structural biology","volume":"150 ","pages":"1-28"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147571803","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}

引用次数: 0

Sticks with whips in neurodegenerative diseases: On the roles of intrinsic disorder in the (dis)function of cytoskeletal proteins. 神经退行性疾病中的鞭子：细胞骨架蛋白功能紊乱的内在紊乱的作用。

3区生物学

Advances in protein chemistry and structural biology Pub Date : 2026-01-01 Epub Date: 2025-11-27 DOI: 10.1016/bs.apcsb.2025.10.031

Swayam Jyothi Tirupathi, Vladimir N Uversky

{"title":"Sticks with whips in neurodegenerative diseases: On the roles of intrinsic disorder in the (dis)function of cytoskeletal proteins.","authors":"Swayam Jyothi Tirupathi, Vladimir N Uversky","doi":"10.1016/bs.apcsb.2025.10.031","DOIUrl":"https://doi.org/10.1016/bs.apcsb.2025.10.031","url":null,"abstract":"Cytoskeleton represents a set of specific proteins uniquely organized in a complex network of protein filaments within cells that has a multitude of crucial roles, acting as a structural framework, facilitating intracellular transport, enabling various cellular processes, such as cell division, intracellular cargo transport, and cell movement, as well as providing mechanical support and maintaining cellular structure. The cytoskeleton is particularly vital in neurons, as their shape, axonal transport, and synaptic transmission are controlled by this complex interacting meshwork. Therefore, it is not surprising that aberrations in cytoskeleton and dysregulations of the neuronal cytoskeletal proteins are linked to a wide spectrum of neurodegenerative diseases. Vast literature exists about physiological and pathological roles of neuronal cytoskeleton. It is clear that the specific structural organization of different cytoskeletal forms and associated distinctive sets of specific functions and dysfunctions are determined by the proteins forming specific filaments (microfilaments, microtubules, and intermediate filaments) and by the proteins interacting with those filament formers. Therefore, one deals here with large and complex proteinaceous machines composed of multiple highly diversified components. Commonly, multifunctionality and complexity of proteins are associated with the intrinsic disorder phenomenon. Analysis of such structure-disorder-function connections in neuronal cytoskeleton represents a subject of this study. We are showing here that the overall organization of the elements of the neuronal cytoskeleton represents an intertwined unity of order and disorder and can be described as supramolecular sticks with whips assembled from macromolecular sticks with whips.","PeriodicalId":7376,"journal":{"name":"Advances in protein chemistry and structural biology","volume":"150 ","pages":"29-118"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147571862","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}

引用次数: 0

Antimicrobial peptides act as a component of brain immunity against microbes in Alzheimer's disease. 在阿尔茨海默病中，抗菌肽是大脑对微生物免疫的一个组成部分。

3区生物学

Advances in protein chemistry and structural biology Pub Date : 2026-01-01 Epub Date: 2025-11-08 DOI: 10.1016/bs.apcsb.2025.10.016

Madhura Chandrashekar, Gowshika Velmurugan, Amit Mishra, Subashchandrabose Chinnathambi

{"title":"Antimicrobial peptides act as a component of brain immunity against microbes in Alzheimer's disease.","authors":"Madhura Chandrashekar, Gowshika Velmurugan, Amit Mishra, Subashchandrabose Chinnathambi","doi":"10.1016/bs.apcsb.2025.10.016","DOIUrl":"https://doi.org/10.1016/bs.apcsb.2025.10.016","url":null,"abstract":"Alzheimer's disease is a most prevalent type of dementia in elderly people. Extracellular accumulation of Amyloid-β (Aβ) and intracellular aggregation of Tau NFTs in the brain is proposed to be a key factor in the development of Alzheimer's disease. A fast-growing body of evidence strengthened the infectious hypothesis of sporadic type of AD. Recent clinical studies focused on the characterizing of antimicrobial peptides (AMPs), because it has been documented that some pathogenic microorganism, such as herpesviruses and particular bacterial strains, are generally present in AD individuals. And also, the environmental factors, such as persistent bacterial or viral infections, change the blood-brain barrier's (BBB) permeability, making it easier for opportunistic pathogens to colonise the brain. This review highlights the potential role of Aβ, which perform antimicrobial activity against diverse pathogens, significantly encouraging its role in the innate immune response. While mammalian amyloid is linked with disease, numerous microbes form amyloid fibrils to embattle the biofilm that prevent the cells from the surrounding environment. According to the microbial AD hypothesis, Aβ clumps up to combat the microbial infection.","PeriodicalId":7376,"journal":{"name":"Advances in protein chemistry and structural biology","volume":"149 ","pages":"395-418"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146045996","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}

引用次数: 0

Unraveling the role of antimicrobial proteins in leptospirosis: A comprehensive transcriptomic analysis. 揭示抗菌蛋白在钩端螺旋体病中的作用：一项全面的转录组分析。

3区生物学

Advances in protein chemistry and structural biology Pub Date : 2026-01-01 Epub Date: 2025-05-30 DOI: 10.1016/bs.apcsb.2024.11.015

Nivedya Kottarath, Megha Hari, Prasanna Kumar Selvam, Karthick Vasudevan

{"title":"Unraveling the role of antimicrobial proteins in leptospirosis: A comprehensive transcriptomic analysis.","authors":"Nivedya Kottarath, Megha Hari, Prasanna Kumar Selvam, Karthick Vasudevan","doi":"10.1016/bs.apcsb.2024.11.015","DOIUrl":"https://doi.org/10.1016/bs.apcsb.2024.11.015","url":null,"abstract":"Leptospirosis, caused by Leptospira bacteria, poses a significant global health threat with notable mortality rates. This study employs advanced transcriptomics to explore the complex interactions between host and pathogen, focusing on antimicrobial peptides (AMPs). Genomic data from mice infected with various Leptospira serotypes underwent rigorous quality control, alignment to the Mus musculus genome, and quantification using FeatureCounts. DESeq2 analysis revealed 491 differentially expressed genes (DEGs), shedding light on key molecular pathways crucial to leptospirosis pathogenesis, particularly involving AMP resistance mechanisms. Important molecular functions, KEGG pathways, cellular components, and biological processes linked to AMP resistance were revealed by functional enrichment analysis. These findings underscore roles in stress responses, immune modulation, and stimulus regulation. Utilizing Cytoscape, a protein-protein interaction network identified pivotal hub proteins such as Ptprc, Stat3, Syk, Stat5a, Stat1, Il18, Fcgr3, Jak2, Sell, and Jak1, integral to immune responses, signaling cascades, and cellular processes essential for AMP resistance. This comprehensive analysis provides valuable insights into the mechanisms underlying AMP resistance in leptospirosis. The identified biomarkers hold promise for developing targeted diagnostic tools and therapeutic strategies to combat AMP-resistant leptospirosis strains, potentially alleviating its global health impact. Further validation and comprehensive exploration are crucial to advancing our understanding and enhancing patient care strategies against antimicrobial resistance in leptospirosis.","PeriodicalId":7376,"journal":{"name":"Advances in protein chemistry and structural biology","volume":"149 ","pages":"333-352"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146045909","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}

引用次数: 0

G-protein coupled receptor regulates cytoskeletal remodelling of extracellular Tau in Alzheimer's disease. g蛋白偶联受体调控阿尔茨海默病中细胞外Tau的细胞骨架重塑。

3区生物学

Advances in protein chemistry and structural biology Pub Date : 2026-01-01 Epub Date: 2025-11-20 DOI: 10.1016/bs.apcsb.2025.10.018

Subashchandrabose Chinnathambi, Nagaraj Rangappa, Gowshika Velmurugan, Madhura Chandrashekar

引用次数: 0

Computational structure-based evaluation of antimicrobial peptides against OXA-51 β-lactamase in carbapenem-resistant Acinetobacter baumannii. 基于计算结构的抗碳青霉烯耐药鲍曼不动杆菌OXA-51 β-内酰胺酶抗菌肽评价。

3区生物学

Advances in protein chemistry and structural biology Pub Date : 2026-01-01 Epub Date: 2025-12-03 DOI: 10.1016/bs.apcsb.2025.09.003

Mohanraj Gopikrishnan, George Priya Doss C

{"title":"Computational structure-based evaluation of antimicrobial peptides against OXA-51 β-lactamase in carbapenem-resistant Acinetobacter baumannii.","authors":"Mohanraj Gopikrishnan, George Priya Doss C","doi":"10.1016/bs.apcsb.2025.09.003","DOIUrl":"https://doi.org/10.1016/bs.apcsb.2025.09.003","url":null,"abstract":"Antimicrobial peptides (AMPs) constitute a promising class of next-generation therapeutics, exhibiting broad-spectrum efficacy and a diminished propensity for inducing resistance. Recent strides in computational biology have facilitated the rational design and high-throughput screening of AMPs tailored to target specific resistance mechanisms. In this study, we employed a structure-guided computational pipeline to identify and prioritize AMPs with inhibitory potential against OXA-51 β-lactamase, a pivotal enzyme contributing to carbapenem resistance in Acinetobacter baumannii. A comprehensive dataset comprising 300 AMPs, 250 of natural origin, and 50 synthetically engineered was curated through meta-analytical approaches. These peptides were systematically filtered based on key parameters, including physicochemical attributes, predicted toxicity, proteolytic stability, and aqueous solubility. Subsequent molecular docking analyses enabled the identification of eight high-affinity candidates, with AMP219 (NRC12), emerging as the top performer, exhibiting a binding energy of -214.98 kcal/mol. To further validate the binding stability and dynamic behavior of the AMP219 with the OXA-51 complex, a 300-nanosecond molecular dynamics simulation (MDS) was conducted. The results revealed sustained intermolecular interactions, persistent hydrogen bonding, and notable conformational rearrangements within the enzyme's active site, underscoring the peptide's inhibitory potential. Collectively, these findings emphasize the utility of integrative computational strategies in accelerating peptide-based drug discovery and provide a robust foundation for subsequent experimental validation against multidrug-resistant pathogens.","PeriodicalId":7376,"journal":{"name":"Advances in protein chemistry and structural biology","volume":"149 ","pages":"61-92"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146045881","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}

引用次数: 0

Unlocking the power of antimicrobial peptides to combat infectious agents. 释放抗菌肽对抗感染因子的力量。

3区生物学

Advances in protein chemistry and structural biology Pub Date : 2026-01-01 Epub Date: 2025-05-30 DOI: 10.1016/bs.apcsb.2024.11.013

Takhellambam Malemnganba, Kirti Baghel, Sanjana Mehrotra, Vijay Kumar Prajapati

{"title":"Unlocking the power of antimicrobial peptides to combat infectious agents.","authors":"Takhellambam Malemnganba, Kirti Baghel, Sanjana Mehrotra, Vijay Kumar Prajapati","doi":"10.1016/bs.apcsb.2024.11.013","DOIUrl":"https://doi.org/10.1016/bs.apcsb.2024.11.013","url":null,"abstract":"The rapid rise of antibiotic-resistant bacteria has become a major clinical challenge, creating an urgent need for alternative therapeutic strategies. Antimicrobial peptides (AMPs) have emerged as promising candidates in the fight against these resistant pathogens. Naturally produced by a wide variety of organisms, AMPs are a crucial part of the innate immune system, offering a broad-spectrum antimicrobial effect against bacteria, fungi, viruses, and parasites. Unlike traditional antibiotics, AMPs primarily target microbial membranes, which reduces the likelihood of resistance development. Beyond their pathogen-destroying properties, AMPs enhance immune responses, aid in wound healing, and exhibit anticancer properties. Their ability to act swiftly and in synergy with the host immune system offers a distinct advantage over conventional antibiotics. Furthermore, AMPs hold the potential to be developed into novel treatments for infections that have become resistant to all available therapies. However, bacterial resistance mechanisms to AMPs-such as membrane modifications, protease production, and biofilm formation-underscore the complex interactions between hosts and pathogens. Despite these challenges, AMPs present an exciting avenue across multiple sectors, including medicine, agriculture, and food safety. Recent research also highlights their potential in treating viral infections, including COVID-19, showcasing their versatile applications. This chapter discusses the role of AMPs in addressing antibiotic resistance, their mechanisms of action, and their diverse therapeutic applications beyond bacterial infections.","PeriodicalId":7376,"journal":{"name":"Advances in protein chemistry and structural biology","volume":"149 ","pages":"203-244"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146045952","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}

引用次数: 0