編譯 | 馮維維
Science, 17 Mar 2023,Volume 379 Issue 6637
《科學》，2023年3月17日，第379卷6637期
生物學Biology
Evolutionary transitions from camouflage to aposematism: Hidden signals play a pivotal role
從偽裝到警示的進化轉變：隱藏信號起關鍵作用
▲ 作者：KARL LOEFFLER-HENRY, CHANGKU KANG , AND THOMAS N. SHERRATT
▲ 連結：
https://www.science.org/doi/10.1126/science.ade5156
▲ 摘要：
用鮮艷的顏色來警告或警示捕食者遠離有毒的獵物，是進化中的一個悖論。顏色鮮艷的生物比善於偽裝的同類更容易被捕食，它們如何存活足夠長的時間並對捕食者形成警告呢？
作者對兩棲動物抗捕食著色的進化轉變進行了大規模分析，證明了從偽裝到警示的進化轉變很少是直接的，但往往涉及一個中間階段，即兼性地顯示顯著著色的隱色物種。解釋這一中間步驟可以解決悖論，促進人們對警示語演變的理解。
▲ 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
巨型泛素連接酶BIRC6介導的拮抗抑制的結構基礎
▲ 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
▲ 連結：
https://www.science.org/doi/10.1126/science.ade8873
▲ 摘要：
泛素連接酶BIRC6是一種凋亡抑制劑（IAP）。在正常情況下，它結合到凋亡蛋白酶，並靶向這些蛋白質降解，防止細胞死亡。這種機制可以被癌細胞所利用，癌細胞經常上調IAPs。
研究者展示了BIRC6複合物的互補結構，闡明了該關鍵蛋白介導細胞凋亡控制的分子機制。BIRC6採用二聚體的馬蹄形結構，具有一個中心腔，允許與目標蛋白酶結合。
促凋亡蛋白SMAC通過多種相互作用與蛋白酶緊密結合在同一內部位點，本質上不可逆地阻斷BIRC6結合底物的能力。這三項研究中的結構和支持的生化工作為細胞凋亡和自噬這一關鍵「看門人」的功能提供了豐富的見解。
▲ 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
半胱氨酸羧乙基化產生新抗原誘導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
▲ 連結：
https://www.science.org/toc/science/current
▲ 摘要：
自身免疫可由破壞免疫耐受的新抗原引起。研究者分析了強直性脊柱炎（一種自身免疫性疾病）患者的蛋白質翻譯後修飾。他們發現整合素αIIb的半胱氨酸殘基在需要腸道微生物代謝物3-羥基丙酸（3-HPA）的過程中被羧乙化，並導致致病性新抗原。用修飾過的蛋白或3-HPA處理HLA-DR4小鼠會產生自身抗體和自身免疫病理。
▲ 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.
化學Chemistry
Chemical scissor–mediated structural editing of layered transition metal carbides
化學剪刀介導的層狀過渡金屬碳化物的結構編輯
▲ 作者：HAOMING DING, YOUBING LI, MIAN LI, KE CHEN, KUN LIANG, GUOXIN CHEN, JUN LU, JUSTINAS PALISAITIS, PER O. Å. PERSSON, AND QING HUANG
▲ 連結：
https://www.science.org/doi/10.1126/science.add5901
▲ 摘要：
插層材料具有獨特的性能，可作為重要的二維材料的前體。然而，非范德華結構的插層很難擴展二維材料家族。作者報導了一種層狀碳化物（MAX相）及其二維衍生物（MXenes）的結構編輯協議。
化學剪刀和插層劑分別介導了縫隙打開和物種插層階段，形成了具有非常規元素和結構的MAX相以及具有多功能末端的MXenes。
用金屬剪刀去除MXenes中的末端，然後用原子插入拼接二維碳化物納米片，從而重建MAX相和一系列金屬插入的二維碳化物，這兩者都可能推動從能源到印刷電子等領域的發展。
▲ 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.
微生物學Microbiology
Bacteria require phase separation for fitness in the mammalian gut
細菌需要相分離才能在哺乳動物腸道中存活
▲ 作者：EMILIA KRYPOTOU, GUY E. TOWNSEND II, XIAOHUI GAO, SHOICHI TACHIYAMA, JUN LIU, NICK D. POKORZYNSKI, ANDREW L. GOODMAN, AND EDUARDO A. GROISMAN
▲ 連結：
https://www.science.org/doi/10.1126/science.abn7229
▲ 摘要：
腸道菌群對人類健康至關重要。了解有益細菌如何在腸道中定植，有助於促進腸道健康的醫療干預。作者發現了一種增強腸道共生細菌適應性的機制。擬桿菌（Bacteroides thetaotaomicron）對營養限制和哺乳動物腸道環境的反應是通過將一個轉錄因子隔離在一個無膜室中。
這種分子凝結增加了轉錄因子的活性，並修改了數百個基因的轉錄，包括幾個促進腸道健康的基因。因此，共生菌可以利用蛋白質冷凝來定植哺乳動物宿主。
▲ 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.
生物信息學Bioinformatics
Evolutionary-scale prediction of atomic-level protein structure with a language model
用語言模型預測原子級蛋白質結構的進化尺度
▲ 作者：ZEMING LIN, HALIL AKIN, ROSHAN RAO, BRIAN HIE, ZHONGKAI ZHU, WENTING LU, NIKITA SMETANIN, ROBERT VERKUIL, ORI KABELI, AND ALEXANDER RIVES
▲ 連結：
https://www.science.org/doi/10.1126/science.ade2574
▲ 摘要：
機器學習的最新進展利用多個序列比對中的進化信息來預測蛋白質結構。作者使用大型語言模型演示了從初級序列直接推斷全原子級蛋白質結構。
隨著蛋白質序列的語言模型被放大到150億個參數，在學習的表示中出現了蛋白質結構的原子解析度圖像。這導致高解析度結構預測的數量級加速，使得宏基因組蛋白質的大規模結構表徵成為可能。
作者利用這一能力構建了ESM宏基因組圖譜，預測> 6.17億個宏基因組蛋白質序列的結構，其中> 2.25億個序列的預測具有很高的置信度，使人們可以看到天然蛋白質的廣泛廣度和多樣性。
▲ 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.