《科学》一周（20230317）论文导读
2023/3/19 20:01:12 科学网

     编译 | 冯维维

     Science, 17 Mar 2023,Volume 379 Issue 6637

     《科学》，2023年3月17日，第379卷6637期

    

    

     生物学Biology

     Evolutionary transitions from camouflage to aposematism: Hidden signals play a pivotal role

     从伪装到警示的进化转变：隐藏信号起关键作用

     ▲ 作者：KARL LOEFFLER-HENRY, CHANGKU KANG , AND THOMAS N. SHERRATT

     ▲ 链接：

     https://www.science.org/doi/10.1126/science.ade5156

     ▲ 摘要：

     用鲜艳的颜色来警告或警示捕食者远离有毒的猎物，是进化中的一个悖论。颜色鲜艳的生物比善于伪装的同类更容易被捕食，它们如何存活足够长的时间并对捕食者形成警告呢？

     作者对两栖动物抗捕食着色的进化转变进行了大规模分析，证明了从伪装到警示的进化转变很少是直接的，但往往涉及一个中间阶段，即兼性地显示显著着色的隐色物种。解释这一中间步骤可以解决悖论，促进人们对警示语演变的理解。

     ▲ Abstract：

     Using bright coloration to warn predators off of toxic prey, or aposematism, presents a conundrum in evolution. How do brightly colored organisms survive long enough to warn predators when they are easier to predate than their cryptic peers? Here, we present a large-scale analysis of evolutionary transitions in amphibian antipredation coloration and demonstrate that the evolutionary transition from camouflage to aposematism is rarely direct but tends to involve an intermediary stage, namely cryptic species that facultatively reveal conspicuous coloration. Accounting for this intermediate step can resolve the paradox and thereby advance our understanding of the evolution of aposematism.

     Structural basis for SMAC-mediated antagonism of caspase inhibition by the giant ubiquitin ligase BIRC6

     巨型泛素连接酶BIRC6介导的拮抗抑制的结构基础

     ▲ 作者：LARISSA DIETZ, CARA J. ELLISON, CARLOS RIECHMANN, C. KEITH CASSIDY, F. DANIEL FELFOLDI, ADáN PINTO-FERNáNDEZ, BENEDIKT M. KESSLER, AND PAUL R. ELLIOTT

     ▲ 链接：

     https://www.science.org/doi/10.1126/science.ade8873

     ▲ 摘要：

     泛素连接酶BIRC6是一种凋亡抑制剂(IAP)。在正常情况下，它结合到凋亡蛋白酶，并靶向这些蛋白质降解，防止细胞死亡。这种机制可以被癌细胞所利用，癌细胞经常上调IAPs。

     研究者展示了BIRC6复合物的互补结构，阐明了该关键蛋白介导细胞凋亡控制的分子机制。BIRC6采用二聚体的马蹄形结构，具有一个中心腔，允许与目标蛋白酶结合。

     促凋亡蛋白SMAC通过多种相互作用与蛋白酶紧密结合在同一内部位点，本质上不可逆地阻断BIRC6结合底物的能力。这三项研究中的结构和支持的生化工作为细胞凋亡和自噬这一关键“看门人”的功能提供了丰富的见解。

     ▲ Abstract：

     The ubiquitin ligase BIRC6 is an inhibitor of apoptosis (IAP). Under normal conditions, it binds to apoptotic proteases and targets these proteins for degradation, preventing cell death. This mechanism can be co-opted by cancer cells, which frequently up-regulate IAPs. Hunkeler et al., Dietz et al., and Ehrmann et al. present complementary structures of BIRC6 complexes that illustrate the molecular mechanisms by which this key protein mediates control of apoptosis. BIRC6 adopts a dimeric, horseshoe-shaped architecture with a central cavity that allows for binding to target proteases. The pro-apoptotic protein SMAC binds very tightly to the same interior site as the proteases through multiple interactions, essentially irreversibly blocking the ability of BIRC6 to bind substrates. The structures and supporting biochemical work in these three studies provide rich insights into the functioning of this crucial gatekeeper of apoptosis and autophagy.

     Cysteine carboxyethylation generates neoantigens to induce HLA-restricted autoimmunity

     半胱氨酸羧乙基化产生新抗原诱导HLA限制性自身免疫

     ▲ 作者：Yue Zhai, Liang Chen, Qian Zhao, Zhao-Hui Zheng , Zhi-Nan Chen, Huijie Bian, Xu Yang, Huan-Yu Lu, Peng Lin , and Ping Zhu

     ▲ 链接：

     https://www.science.org/toc/science/current

     ▲ 摘要：

     自身免疫可由破坏免疫耐受的新抗原引起。研究者分析了强直性脊柱炎(一种自身免疫性疾病)患者的蛋白质翻译后修饰。他们发现整合素αIIb的半胱氨酸残基在需要肠道微生物代谢物3-羟基丙酸(3-HPA)的过程中被羧乙化，并导致致病性新抗原。用修饰过的蛋白或3-HPA处理HLA-DR4小鼠会产生自身抗体和自身免疫病理。

     ▲ Abstract：

     Autoimmunity can be caused by neoantigens that break immune tolerance. Zhai et al. profiled protein posttranslational modifications in patients with ankylosing spondylitis, an autoimmune disease. They found that that a cysteine residue of integrin αIIb was carboxyethylated in a process that required the gut microbe metabolite 3-hydroxypropionic acid (3-HPA) and resulted in pathogenic neoantigens. Treatment of HLA-DR4 mice with either the modified protein or 3-HPA resulted in autoantibody production and autoimmune pathology.

     化学Chemistry

     Chemical scissor–mediated structural editing of layered transition metal carbides

     化学剪刀介导的层状过渡金属碳化物的结构编辑

     ▲ 作者：HAOMING DING, YOUBING LI, MIAN LI, KE CHEN, KUN LIANG, GUOXIN CHEN, JUN LU, JUSTINAS PALISAITIS, PER O. ?. PERSSON, AND QING HUANG

     ▲ 链接：

     https://www.science.org/doi/10.1126/science.add5901

     ▲ 摘要：

     插层材料具有独特的性能，可作为重要的二维材料的前体。然而，非范德华结构的插层很难扩展二维材料家族。作者报道了一种层状碳化物(MAX相)及其二维衍生物(MXenes)的结构编辑协议。

     化学剪刀和插层剂分别介导了缝隙打开和物种插层阶段，形成了具有非常规元素和结构的MAX相以及具有多功能末端的MXenes。

     用金属剪刀去除MXenes中的末端，然后用原子插入拼接二维碳化物纳米片，从而重建MAX相和一系列金属插入的二维碳化物，这两者都可能推动从能源到印刷电子等领域的发展。

     ▲ Abstract：

     Intercalated layered materials offer distinctive properties and serve as precursors for important two-dimensional (2D) materials. However, intercalation of non–van der Waals structures, which can expand the family of 2D materials, is difficult. We report a structural editing protocol for layered carbides (MAX phases) and their 2D derivatives (MXenes). Gap-opening and species-intercalating stages were respectively mediated by chemical scissors and intercalants, which created a large family of MAX phases with unconventional elements and structures, as well as MXenes with versatile terminals. The removal of terminals in MXenes with metal scissors and then the stitching of 2D carbide nanosheets with atom intercalation leads to the reconstruction of MAX phases and a family of metal-intercalated 2D carbides, both of which may drive advances in fields ranging from energy to printed electronics.

     微生物学Microbiology

     Bacteria require phase separation for fitness in the mammalian gut

     细菌需要相分离才能在哺乳动物肠道中存活

     ▲作者：EMILIA KRYPOTOU, GUY E. TOWNSEND II, XIAOHUI GAO, SHOICHI TACHIYAMA, JUN LIU, NICK D. POKORZYNSKI, ANDREW L. GOODMAN, AND EDUARDO A. GROISMAN

     ▲ 链接：

     https://www.science.org/doi/10.1126/science.abn7229

     ▲ 摘要：

     肠道菌群对人类健康至关重要。了解有益细菌如何在肠道中定植，有助于促进肠道健康的医疗干预。作者发现了一种增强肠道共生细菌适应性的机制。拟杆菌(Bacteroides thetaotaomicron)对营养限制和哺乳动物肠道环境的反应是通过将一个转录因子隔离在一个无膜室中。

     这种分子凝结增加了转录因子的活性，并修改了数百个基因的转录，包括几个促进肠道健康的基因。因此，共生菌可以利用蛋白质冷凝来定植哺乳动物宿主。

     ▲ Abstract：

     The gut microbiota is critical for human health. Understanding how beneficial bacteria colonize the gut enables medical interventions that promote gut health. Krypotou et al. discovered a mechanism that enhances the fitness of a commensal bacterium in the gut. Bacteroides thetaiotaomicron responded to nutrient limitation and the mammalian gut environment by sequestering a transcription factor within a membraneless compartment. This molecular condensation increased transcription factor activity and modified the transcription of hundreds of genes, including several promoting gut fitness. Thus, commensal bacteria can exploit protein condensation to colonize mammalian hosts.

     生物信息学Bioinformatics

     Evolutionary-scale prediction of atomic-level protein structure with a language model

     用语言模型预测原子级蛋白质结构的进化尺度

     ▲ 作者：ZEMING LIN, HALIL AKIN, ROSHAN RAO, BRIAN HIE, ZHONGKAI ZHU, WENTING LU, NIKITA SMETANIN, ROBERT VERKUIL, ORI KABELI, AND ALEXANDER RIVES

     ▲ 链接：

     https://www.science.org/doi/10.1126/science.ade2574

     ▲ 摘要：

     机器学习的最新进展利用多个序列比对中的进化信息来预测蛋白质结构。作者使用大型语言模型演示了从初级序列直接推断全原子级蛋白质结构。

     随着蛋白质序列的语言模型被放大到150亿个参数，在学习的表示中出现了蛋白质结构的原子分辨率图像。这导致高分辨率结构预测的数量级加速，使得宏基因组蛋白质的大规模结构表征成为可能。

     作者利用这一能力构建了ESM宏基因组图谱，预测> 6.17亿个宏基因组蛋白质序列的结构，其中> 2.25亿个序列的预测具有很高的置信度，使人们可以看到天然蛋白质的广泛广度和多样性。

     ▲ Abstract：

     Recent advances in machine learning have leveraged evolutionary information in multiple sequence alignments to predict protein structure. We demonstrate direct inference of full atomic-level protein structure from primary sequence using a large language model. As language models of protein sequences are scaled up to 15 billion parameters, an atomic-resolution picture of protein structure emerges in the learned representations. This results in an order-of-magnitude acceleration of high-resolution structure prediction, which enables large-scale structural characterization of metagenomic proteins. We apply this capability to construct the ESM Metagenomic Atlas by predicting structures for >617 million metagenomic protein sequences, including >225 million that are predicted with high confidence, which gives a view into the vast breadth and diversity of natural proteins.

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