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Structural Mechanisms for Replicating DNA in Eukaryotes. 真核生物DNA复制的结构机制。
IF 16.6 1区 生物学 Q1 Biochemistry, Genetics and Molecular Biology Pub Date : 2021-06-20 Epub Date: 2021-03-30 DOI: 10.1146/annurev-biochem-090120-125407
Ilan Attali, Michael R Botchan, James M Berger
The faithful and timely copying of DNA by molecular machines known as replisomes depends on a disparate suite of enzymes and scaffolding factors working together in a highly orchestrated manner. Large, dynamic protein-nucleic acid assemblies that selectively morph between distinct conformations and compositional states underpin this critical cellular process. In this article, we discuss recent progress outlining the physical basis of replisome construction and progression in eukaryotes. Expected final online publication date for the Annual Review of Biochemistry, Volume 90 is June 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.
被称为复制体的分子机器忠实而及时地复制DNA依赖于一套完全不同的酶和支架因子以一种高度协调的方式协同工作。在不同构象和组成状态之间选择性变形的大型动态蛋白质核酸组装支撑着这一关键的细胞过程。在这篇文章中,我们讨论了最近的进展概述了真核生物的复制体建设和进展的物理基础。
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引用次数: 21
Mechanisms for Regulating and Organizing Receptor Signaling by Endocytosis. 内吞作用调节和组织受体信号传导的机制。
IF 16.6 1区 生物学 Q1 Biochemistry, Genetics and Molecular Biology Pub Date : 2021-06-20 Epub Date: 2021-02-19 DOI: 10.1146/annurev-biochem-081820-092427
Mark von Zastrow, Alexander Sorkin

Intricate relationships between endocytosis and cellular signaling, first recognized nearly 40 years ago through the study of tyrosine kinase growth factor receptors, are now known to exist for multiple receptor classes and to affect myriad physiological and developmental processes. This review summarizes our present understanding of how endocytosis orchestrates cellular signaling networks, with an emphasis on mechanistic underpinnings and focusing on two receptor classes-tyrosine kinase and G protein-coupled receptors-that have been investigated in particular detail. Together, these examples provide a useful survey of the current consensus, uncertainties, and controversies in this rapidly advancing area of cell biology.

近40年前,通过对酪氨酸激酶生长因子受体的研究,首次认识到内吞作用和细胞信号传导之间的复杂关系,现在已知存在于多种受体类别中,并影响无数的生理和发育过程。这篇综述总结了我们目前对内吞作用如何协调细胞信号网络的理解,重点是机制基础,并关注两类受体-酪氨酸激酶和G蛋白偶联受体-已经进行了详细的研究。总之,这些例子提供了一个有用的调查,当前的共识,不确定性和争议在这个快速发展的细胞生物学领域。
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引用次数: 36
Tunnels for Protein Export from the Endoplasmic Reticulum. 内质网蛋白质输出通道。
IF 16.6 1区 生物学 Q1 Biochemistry, Genetics and Molecular Biology Pub Date : 2021-06-20 Epub Date: 2021-01-27 DOI: 10.1146/annurev-biochem-080120-022017
I Raote, V Malhotra

The functions of coat protein complex II (COPII) coats in cargo packaging and the creation of vesicles at the endoplasmic reticulum are conserved in eukaryotic protein secretion. Standard COPII vesicles, however, cannot handle the secretion of metazoan-specific cargoes such as procollagens, apolipoproteins, and mucins. Metazoans have thus evolved modules centered on proteins like TANGO1 (transport and Golgi organization 1) to engage COPII coats and early secretory pathway membranes to engineer a novel mode of cargo export at the endoplasmic reticulum.

在真核生物蛋白分泌过程中,货物包装中的外壳蛋白复合物II (COPII)的功能和内质网囊泡的形成是保守的。然而,标准的COPII囊泡不能处理后生动物特异性货物的分泌,如前胶原、载脂蛋白和粘蛋白。因此,后生动物进化出了以TANGO1(运输和高尔基组织1)等蛋白质为中心的模块,以参与COPII外壳和早期分泌途径膜,以设计一种新的内质网货物出口模式。
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引用次数: 32
Preparing Better Samples for Cryo-Electron Microscopy: Biochemical Challenges Do Not End with Isolation and Purification. 制备更好的样品冷冻电子显微镜:生化挑战不结束与分离和纯化。
IF 16.6 1区 生物学 Q1 Biochemistry, Genetics and Molecular Biology Pub Date : 2021-06-20 Epub Date: 2021-02-08 DOI: 10.1146/annurev-biochem-072020-020231
Robert M Glaeser

The preparation of extremely thin samples, which are required for high-resolution electron microscopy, poses extreme risk of damaging biological macromolecules due to interactions with the air-water interface. Although the rapid increase in the number of published structures initially gave little indication that this was a problem, the search for methods that substantially mitigate this hazard is now intensifying. The two main approaches under investigation are (a) immobilizing particles onto structure-friendly support films and (b) reducing the length of time during which such interactions may occur. While there is little possibility of outrunning diffusion to the interface, intentional passivation of the interface may slow the process of adsorption and denaturation. In addition, growing attention is being given to gaining more effective control of the thickness of the sample prior to vitrification.

高分辨率电子显微镜所需要的极薄样品的制备,由于与空气-水界面的相互作用,造成了破坏生物大分子的极大风险。虽然发表的结构数量的迅速增加最初并没有显示出这是一个问题,但现在正在加紧寻找实质性减轻这种危害的方法。正在研究的两种主要方法是(a)将颗粒固定在结构友好的支撑膜上和(b)减少这种相互作用可能发生的时间长度。虽然逃逸扩散到界面的可能性很小,但有意的界面钝化可能会减缓吸附和变性的过程。此外,在玻璃化前对样品的厚度进行更有效的控制也受到越来越多的关注。
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引用次数: 21
Structural Mechanism of Transport of Mitochondrial Carriers. 线粒体载体运输的结构机制。
IF 16.6 1区 生物学 Q1 Biochemistry, Genetics and Molecular Biology Pub Date : 2021-06-20 Epub Date: 2021-02-08 DOI: 10.1146/annurev-biochem-072820-020508
J J Ruprecht, E R S Kunji

Members of the mitochondrial carrier family [solute carrier family 25 (SLC25)] transport nucleotides, amino acids, carboxylic acids, fatty acids, inorganic ions, and vitamins across the mitochondrial inner membrane. They are important for many cellular processes, such as oxidative phosphorylation of lipids and sugars, amino acid metabolism, macromolecular synthesis, ion homeostasis, cellular regulation, and differentiation. Here, we describe the functional elements of the transport mechanism of mitochondrial carriers, consisting of one central substrate-binding site and two gates with salt-bridge networks on either side of the carrier. Binding of the substrate during import causes three gate elements to rotate inward, forming the cytoplasmic network and closing access to the substrate-binding site from the intermembrane space. Simultaneously, three core elements rock outward, disrupting the matrix network and opening the substrate-binding site to the matrix side of the membrane. During export, substrate binding triggers conformational changes involving the same elements but operating in reverse.

线粒体载体家族成员[溶质载体家族25 (SLC25)]通过线粒体内膜运输核苷酸、氨基酸、羧酸、脂肪酸、无机离子和维生素。它们对许多细胞过程都很重要,如脂质和糖的氧化磷酸化、氨基酸代谢、大分子合成、离子稳态、细胞调节和分化。在这里,我们描述了线粒体载体运输机制的功能要素,包括一个中心底物结合位点和两个在载体两侧具有盐桥网络的门。在导入过程中,底物的结合导致三个门元件向内旋转,形成细胞质网络并关闭从膜间空间进入底物结合位点的通道。同时,三个核心元素向外晃动,破坏基质网络,打开基质结合位点到膜的基质侧。在导出过程中,底物结合触发构象变化,涉及相同的元素,但反向操作。
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引用次数: 23
An Overview of Microcrystal Electron Diffraction (MicroED). 微晶电子衍射(MicroED)综述。
IF 16.6 1区 生物学 Q1 Biochemistry, Genetics and Molecular Biology Pub Date : 2021-06-20 DOI: 10.1146/annurev-biochem-081720-020121
Xuelang Mu, Cody Gillman, Chi Nguyen, Tamir Gonen

The bedrock of drug discovery and a key tool for understanding cellular function and drug mechanisms of action is the structure determination of chemical compounds, peptides, and proteins. The development of new structure characterization tools, particularly those that fill critical gaps in existing methods, presents important steps forward for structural biology and drug discovery. The emergence of microcrystal electron diffraction (MicroED) expands the application of cryo-electron microscopy to include samples ranging from small molecules and membrane proteins to even large protein complexes using crystals that are one-billionth the size of those required for X-ray crystallography. This review outlines the conception, achievements, and exciting future trajectories for MicroED, an important addition to the existing biophysical toolkit.

药物发现的基础和理解细胞功能和药物作用机制的关键工具是化合物、多肽和蛋白质的结构测定。新的结构表征工具的发展,特别是那些填补了现有方法的关键空白的工具,为结构生物学和药物发现迈出了重要的一步。微晶体电子衍射(MicroED)的出现扩大了低温电子显微镜的应用范围,包括从小分子和膜蛋白到大蛋白质复合物的样品,使用的晶体是x射线晶体学所需尺寸的十亿分之一。这篇综述概述了MicroED的概念、成就和令人兴奋的未来轨迹,MicroED是现有生物物理工具包的重要补充。
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引用次数: 4
Introduction to the Theme on Membrane Channels. 膜通道主题简介。
IF 16.6 1区 生物学 Q1 Biochemistry, Genetics and Molecular Biology Pub Date : 2021-06-20 DOI: 10.1146/annurev-biochem-010421-023239
Gunnar von Heijne

This volume of the Annual Review of Biochemistry contains three reviews on membrane channel proteins: the first by Szczot et al., titled The Form and Function of PIEZO2; the second by Ruprecht & Kunji, titled Structural Mechanism of Transport of Mitochondrial Carriers; and the third by McIlwain et al., titled Membrane Exporters of Fluoride Ion. These reviews provide nice illustrations of just how far evolution has been able to play with the basic helix-bundle architecture of integral membrane proteins to produce membrane channels and transporters of widely different functions.

本卷的生物化学年度评论包含对膜通道蛋白的三个评论:第一个由Szczot等人,标题为PIEZO2的形式和功能;第二篇由Ruprecht & Kunji撰写,题为《线粒体载体运输的结构机制》;第三篇由McIlwain等人撰写,题为《氟离子的膜出口商》。这些综述很好地说明了进化是如何利用完整膜蛋白的基本螺旋束结构产生具有广泛不同功能的膜通道和转运体的。
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引用次数: 1
Membrane Exporters of Fluoride Ion. 氟离子出口膜。
IF 16.6 1区 生物学 Q1 Biochemistry, Genetics and Molecular Biology Pub Date : 2021-06-20 Epub Date: 2021-01-25 DOI: 10.1146/annurev-biochem-071520-112507
Benjamin C McIlwain, Michal T Ruprecht, Randy B Stockbridge

Microorganisms contend with numerous and unusual chemical threats and have evolved a catalog of resistance mechanisms in response. One particularly ancient, pernicious threat is posed by fluoride ion (F-), a common xenobiotic in natural environments that causes broad-spectrum harm to metabolic pathways. This review focuses on advances in the last ten years toward understanding the microbial response to cytoplasmic accumulation of F-, with a special emphasis on the structure and mechanisms of the proteins that microbes use to export fluoride: the CLCF family of F-/H+ antiporters and the Fluc/FEX family of F- channels.

微生物与许多不同寻常的化学威胁作斗争,并已进化出一系列抗性机制作为回应。氟化物离子(F-)是一种特别古老的有害威胁,它是自然环境中常见的一种外生物质,对代谢途径造成广谱损害。本文综述了近十年来在了解微生物对F-细胞质积累的反应方面的进展,特别强调了微生物用于输出氟化物的蛋白质的结构和机制:F-/H+反转运蛋白CLCF家族和F-通道Fluc/FEX家族。
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引用次数: 15
Cullin-RING Ubiquitin Ligase Regulatory Circuits: A Quarter Century Beyond the F-Box Hypothesis. Cullin-RING 泛素连接酶调控回路:F-Box假说之后的四分之一世纪
IF 12.1 1区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2021-06-20 Epub Date: 2021-04-06 DOI: 10.1146/annurev-biochem-090120-013613
J Wade Harper, Brenda A Schulman

Cullin-RING ubiquitin ligases (CRLs) are dynamic modular platforms that regulate myriad biological processes through target-specific ubiquitylation. Our knowledge of this system emerged from the F-box hypothesis, posited a quarter century ago: Numerous interchangeable F-box proteins confer specific substrate recognition for a core CUL1-based RING E3 ubiquitin ligase. This paradigm has been expanded through the evolution of a superfamily of analogous modular CRLs, with five major families and over 200 different substrate-binding receptors in humans. Regulation is achieved by numerous factors organized in circuits that dynamically control CRL activation and substrate ubiquitylation. CRLs also serve as a vast landscape for developing small molecules that reshape interactions and promote targeted ubiquitylation-dependent turnover of proteins of interest. Here, we review molecular principles underlying CRL function, the role of allosteric and conformational mechanisms in controlling substrate timing and ubiquitylation, and how the dynamics of substrate receptor interchange drives the turnover of selected target proteins to promote cellular decision-making.

Cullin-RING 泛素连接酶(CRLs)是一个动态的模块化平台,通过靶标特异性泛素化调控无数生物过程。我们对这一系统的了解源于 25 年前提出的 F-box 假说:大量可互换的 F-box 蛋白赋予基于 CUL1 的核心 RING E3 泛素连接酶特异性底物识别能力。通过类似模块化 CRLs 超家族的进化,这一范式得到了扩展,在人类中有五个主要家族和 200 多种不同的底物结合受体。许多因素组成回路,动态控制 CRL 的激活和底物泛素化,从而实现调控。CRL 也是开发小分子药物的广阔天地,这些小分子药物可重塑相互作用,促进相关蛋白质泛素化依赖性的定向周转。在此,我们回顾了 CRL 功能的分子原理、异构和构象机制在控制底物定时和泛素化中的作用,以及底物受体交换的动态如何驱动选定靶蛋白的周转以促进细胞决策。
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引用次数: 0
Optobiochemistry: Genetically Encoded Control of Protein Activity by Light. 光生物化学:光对蛋白质活性的基因编码控制。
IF 12.1 1区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2021-06-20 Epub Date: 2021-03-29 DOI: 10.1146/annurev-biochem-072420-112431
Jihye Seong, Michael Z Lin

Optobiochemical control of protein activities allows the investigation of protein functions in living cells with high spatiotemporal resolution. Over the last two decades, numerous natural photosensory domains have been characterized and synthetic domains engineered and assembled into photoregulatory systems to control protein function with light. Here, we review the field of optobiochemistry, categorizing photosensory domains by chromophore, describing photoregulatory systems by mechanism of action, and discussing protein classes frequently investigated using optical methods. We also present examples of how spatial or temporal control of proteins in living cells has provided new insights not possible with traditional biochemical or cell biological techniques.

通过光生物化学方法控制蛋白质的活动,可以高时空分辨率地研究活细胞中蛋白质的功能。在过去二十年里,许多天然光感结构域已被表征出来,合成结构域也被工程化并组装成光调节系统,利用光来控制蛋白质的功能。在此,我们回顾了光生物化学领域,按发色团将光感结构域分类,按作用机制描述光调节系统,并讨论了经常使用光学方法研究的蛋白质类别。我们还举例说明了活细胞中蛋白质的空间或时间控制如何提供了传统生化或细胞生物学技术无法实现的新见解。
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引用次数: 0
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Annual review of biochemistry
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