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CellVis2: a conference on visualizing the molecular cell CellVis2:分子细胞可视化会议
IF 11.6 1区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-07-01 DOI: 10.1016/j.tibs.2024.03.013
Ludovic Autin , David S. Goodsell , Ivan Viola , Arthur Olson

In January 2024, a targeted conference, ‘CellVis2’, was held at Scripps Research in La Jolla, USA, the second in a series designed to explore the promise, practices, roadblocks, and prospects of creating, visualizing, sharing, and communicating physical representations of entire biological cells at scales down to the atom.

2024 年 1 月,一场名为 "CellVis2 "的定向会议在美国拉霍亚的斯克里普斯研究所举行,这是系列会议中的第二次会议,旨在探讨创建、可视化、共享和交流整个生物细胞的物理表示(最小到原子)的前景、实践、障碍和展望。
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引用次数: 0
The physiological relevance of autophagosome morphogenesis 自噬体形态发生的生理意义
IF 11.6 1区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-07-01 DOI: 10.1016/j.tibs.2024.05.002
Oren Shatz , Zvulun Elazar

Autophagy sequesters cytoplasmic portions into autophagosomes. While selective cargo is engulfed by elongation of cup-shaped isolation membranes (IMs), the morphogenesis of non-selective IMs remains elusive. Based on recent observations, we propose a novel model for autophagosome morphogenesis wherein active regulation of the IM rim serves the physiological roles of autophagy.

自噬将细胞质部分封存到自噬体中。选择性货物通过杯状隔离膜(IMs)的伸长被吞噬,而非选择性IMs的形态发生仍然难以捉摸。根据最近的观察结果,我们提出了一种新的自噬体形态发生模型,其中对 IM 边缘的主动调控为自噬的生理作用服务。
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引用次数: 0
Optical tweezers microrheology maps micro-mechanics of complex systems 光学镊子微流变学绘制复杂系统的微观力学图。
IF 11.6 1区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-07-01 DOI: 10.1016/j.tibs.2024.04.009
Rae M. Robertson-Anderson
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引用次数: 0
Tyrosine – a structural glue for hierarchical protein assembly 酪氨酸--分层蛋白质组装的结构粘合剂。
IF 11.6 1区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-07-01 DOI: 10.1016/j.tibs.2024.03.014
Anton Maraldo , Jelena Rnjak-Kovacina , Christopher Marquis

Protein self-assembly, guided by the interplay of sequence- and environment-dependent liquid–liquid phase separation (LLPS), constitutes a fundamental process in the assembly of numerous intrinsically disordered proteins. Heuristic examination of these proteins has underscored the role of tyrosine residues, evident in their conservation and pivotal involvement in initiating LLPS and subsequent liquid–solid phase transitions (LSPT). The development of tyrosine-templated constructs, designed to mimic their natural counterparts, emerges as a promising strategy for creating adaptive, self-assembling systems with diverse applications. This review explores the central role of tyrosine in orchestrating protein self-assembly, delving into key interactions and examining its potential in innovative applications, including responsive biomaterials and bioengineering.

在序列和环境依赖性液-液相分离(LLPS)相互作用的引导下,蛋白质的自组装是众多内在无序蛋白质组装的基本过程。对这些蛋白质的启发式研究强调了酪氨酸残基的作用,它们在启动液-液相分离和随后的液-固相变(LSPT)过程中的保守性和关键性显而易见。开发以酪氨酸为模板、旨在模仿天然对应物的构建体,是创造具有多种应用的自适应、自组装系统的一种有前途的策略。这篇综述探讨了酪氨酸在协调蛋白质自组装中的核心作用,深入探讨了关键的相互作用,并研究了其在创新应用中的潜力,包括响应性生物材料和生物工程。
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引用次数: 0
Subscription and Copyright Information 订阅和版权信息
IF 11.6 1区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-07-01 DOI: 10.1016/S0968-0004(24)00142-7
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引用次数: 0
Understanding the dynamic design of the spliceosome 了解剪接体的动态设计。
IF 11.6 1区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-07-01 DOI: 10.1016/j.tibs.2024.03.012
Irene Beusch , Hiten D. Madhani

The spliceosome catalyzes the splicing of pre-mRNAs. Although the spliceosome evolved from a prokaryotic self-splicing intron and an associated protein, it is a vastly more complex and dynamic ribonucleoprotein (RNP) whose function requires at least eight ATPases and multiple RNA rearrangements. These features afford stepwise opportunities for multiple inspections of the intron substrate, coupled with spliceosome disassembly for substrates that fail inspection. Early work using splicing-defective pre-mRNAs or small nuclear (sn)RNAs in Saccharomyces cerevisiae demonstrated that such checks could occur in catalytically active spliceosomes. We review recent results on pre-mRNA splicing in various systems, including humans, suggesting that earlier steps in spliceosome assembly are also subject to such quality control. The inspection–rejection framework helps explain the dynamic nature of the spliceosome.

剪接体催化前 mRNA 的剪接。虽然剪接体是由原核生物自我剪接的内含子和相关蛋白进化而来,但它是一种更为复杂和动态的核糖核蛋白(RNP),其功能至少需要八种 ATP 酶和多种 RNA 重排。这些特点为内含子底物的多次检测提供了逐步进行的机会,同时也为检测失败的底物提供了剪接体分解的机会。早期在酿酒酵母(Saccharomyces cerevisiae)中使用剪接缺陷前mRNA或小核糖核酸(sn)的研究表明,这种检查可以在催化活性剪接体中发生。我们回顾了包括人类在内的各种系统中前 mRNA 剪接的最新结果,表明剪接体组装的早期步骤也会受到这种质量控制的影响。检查-排斥框架有助于解释剪接体的动态性质。
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引用次数: 0
Advisory Board and Contents 咨询委员会和内容
IF 11.6 1区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-07-01 DOI: 10.1016/S0968-0004(24)00139-7
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引用次数: 0
Beneath the surface: endosomal GPCR signaling 表面之下:内体 GPCR 信号传递。
IF 13.8 1区 生物学 Q1 Biochemistry, Genetics and Molecular Biology Pub Date : 2024-06-01 DOI: 10.1016/j.tibs.2024.03.006
Emmanuel Flores-Espinoza , Alex R.B. Thomsen

G protein-coupled receptors (GPCRs) located at the cell surface bind extracellular ligands and convey intracellular signals via activation of heterotrimeric G proteins. Traditionally, G protein signaling was viewed to occur exclusively at this subcellular region followed by rapid desensitization facilitated by β-arrestin (βarr)-mediated G protein uncoupling and receptor internalization. However, emerging evidence over the past 15 years suggests that these βarr-mediated events do not necessarily terminate receptor signaling and that some GPCRs continue to activate G proteins after having been internalized into endosomes. Here, we review the recently elucidated mechanistic basis underlying endosomal GPCR signaling and discuss physiological implications and pharmacological targeting of this newly appreciated signaling mode.

位于细胞表面的 G 蛋白偶联受体(GPCR)与细胞外配体结合,并通过激活异三聚 G 蛋白传递细胞内信号。传统观点认为,G 蛋白信号传导只发生在这一亚细胞区域,随后在 β-阻遏素(βarr)介导的 G 蛋白解偶联和受体内化作用下迅速脱敏。然而,过去 15 年中新出现的证据表明,这些由 βarr 介导的事件并不一定会终止受体信号传导,一些 GPCR 在内化到内体后仍会继续激活 G 蛋白。在此,我们回顾了最近阐明的内泌体 GPCR 信号转导的机理基础,并讨论了这种新近受到重视的信号转导模式的生理意义和药理作用。
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引用次数: 0
Thiol dioxygenases: from structures to functions 硫醇二氧酶:从结构到功能。
IF 13.8 1区 生物学 Q1 Biochemistry, Genetics and Molecular Biology Pub Date : 2024-06-01 DOI: 10.1016/j.tibs.2024.03.007
Monica Perri , Francesco Licausi

Thiol oxidation to dioxygenated sulfinic acid is catalyzed by an enzyme family characterized by a cupin fold. These proteins act on free thiol-containing molecules to generate central metabolism precursors and signaling compounds in bacteria, fungi, and animal cells. In plants and animals, they also oxidize exposed N-cysteinyl residues, directing proteins to proteolysis. Enzyme kinetics, X-ray crystallography, and spectroscopy studies prompted the formulation and testing of hypotheses about the mechanism of action and the different substrate specificity of these enzymes. Concomitantly, the physiological role of thiol dioxygenation in prokaryotes and eukaryotes has been studied through genetic and physiological approaches. Further structural characterization is necessary to enable precise and safe manipulation of thiol dioxygenases (TDOs) for therapeutic, industrial, and agricultural applications.

硫醇氧化成二氧亚硫酸是由一个以杯状蛋白折叠为特征的酶家族催化的。这些蛋白质作用于含游离硫醇的分子,在细菌、真菌和动物细胞中生成中枢代谢前体和信号化合物。在植物和动物中,它们还氧化暴露的 N-半胱氨酰残基,引导蛋白质发生蛋白水解。酶动力学、X 射线晶体学和光谱学研究促使人们提出并测试有关这些酶的作用机制和不同底物特异性的假设。同时,还通过遗传和生理方法研究了硫醇二氧化在原核生物和真核生物中的生理作用。要想精确、安全地操纵硫醇二氧合酶(TDOs)用于治疗、工业和农业,就必须进一步确定其结构特征。
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引用次数: 0
ULK/Atg1: phasing in and out of autophagy ULK/Atg1:分阶段进入和退出自噬。
IF 13.8 1区 生物学 Q1 Biochemistry, Genetics and Molecular Biology Pub Date : 2024-06-01 DOI: 10.1016/j.tibs.2024.03.004
Bo Wang , Gautam Pareek , Mondira Kundu

Autophagy – a highly regulated intracellular degradation process – is pivotal in maintaining cellular homeostasis. Liquid–liquid phase separation (LLPS) is a fundamental mechanism regulating the formation and function of membrane-less compartments. Recent research has unveiled connections between LLPS and autophagy, suggesting that phase separation events may orchestrate the spatiotemporal organization of autophagic machinery and cargo sequestration. The Unc-51-like kinase (ULK)/autophagy-related 1 (Atg1) family of proteins is best known for its regulatory role in initiating autophagy, but there is growing evidence that the functional spectrum of ULK/Atg1 extends beyond autophagy regulation. In this review, we explore the spatial and temporal regulation of the ULK/Atg1 family of kinases, focusing on their recruitment to LLPS-driven compartments, and highlighting their multifaceted functions beyond their traditional role.

自噬是一种受到高度调控的细胞内降解过程,在维持细胞平衡方面起着关键作用。液-液相分离(LLPS)是调节无膜区室形成和功能的基本机制。最近的研究揭示了液-液相分离与自噬之间的联系,表明相分离事件可能协调了自噬机制和货物螯合的时空组织。Unc-51样激酶(ULK)/自噬相关1(Atg1)蛋白家族因其在启动自噬过程中的调控作用而最为人熟知,但越来越多的证据表明,ULK/Atg1的功能范围超出了自噬调控。在这篇综述中,我们探讨了 ULK/Atg1 家族激酶的空间和时间调控,重点是它们被招募到 LLPS 驱动的区室,并强调了它们在传统作用之外的多方面功能。
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引用次数: 0
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Trends in Biochemical Sciences
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