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身為一個熱愛美食、喜歡在城市裡挖掘驚喜的人,臺中公益路一直是我最常出沒的地方之一。這條路可說是「臺中人的美食戰場」,從精緻西餐到創意火鍋,從日式丼飯到義式早午餐,每走幾步,就會有完全不同的特色料理餐廳。 這次我特別花了一整個月,實際造訪了公益路上十間口碑不錯的餐廳。有的是網友熱推的打卡名店,也有隱藏在巷弄裡的小驚喜。我以環境氛圍、口味表現、價格CP值與再訪意願為基準,整理出這篇實測評比。希望能幫正在猶豫去哪裡吃飯的你,找到那一間「吃完會想再來」的餐廳。 評比標準與整理方向
這次我走訪的10家餐廳橫跨不同料理類型,從高質感牛排館到巷弄系早午餐,每一間都有自己獨特的風格。為了讓整體比較更客觀,我依照以下四大面向進行評比,並搭配實際用餐體驗來打分。
整體而言,我希望這份評比不只是「哪家好吃」,而是幫你在不同情境下(約會、家庭聚餐、朋友小聚、商業午餐)都能快速找到合適的選擇。畢竟,美食不只是味覺的滿足,更是一段段與朋友共享的生活記憶。 10間臺中公益路餐廳評比懶人包公益路向來是臺中人聚餐的首選地段,從火鍋、燒肉到中式料理與早午餐,每走幾步就有驚喜。以下是我實際造訪過的10間代表性餐廳清單,橫跨平價、創意、高級各路風格。
一頭牛日式燒肉|炭香濃郁的和牛饗宴,約會聚餐首選
走在公益路上,很難不被 一頭牛日式燒肉 的木質外觀吸引。低調卻不失質感的門面,搭配昏黃燈光與暖色調的內裝,讓人一進門就感受到濃濃的日式職人氛圍。店內空間不大,但桌距規劃得宜,每桌皆設有獨立排煙設備,烤肉時完全不怕滿身油煙味。 餐點特色
一頭牛的靈魂,絕對是他們招牌的「三國和牛拼盤」。 用餐體驗整體節奏掌握得非常好。店員會在你剛想烤下一片肉時貼心遞上夾子、幫忙換烤網,讓人完全不用分心。整場用餐過程就像一場表演,從視覺、嗅覺到味覺都被滿足。 綜合評分
地址:408臺中市南屯區公益路二段162號電話:04-23206800 小結語一頭牛日式燒肉不僅是「吃肉的地方」,更像是一場五感盛宴。從進門那一刻到最後一道甜點,都能感受到他們對細節的用心。 TANG Zhan 湯棧|文青系火鍋代表,麻香湯底與視覺美感並重
在公益路這條美食戰線上,TANG Zhan 湯棧 是讓人一眼就會想走進去的那一種。 餐點特色
湯棧最有名的當然是它的「麻香鍋」。 用餐體驗整體氛圍比一般火鍋店更有質感。 綜合評分
地址:408臺中市南屯區公益路二段248號電話:04-22580617 官網:https://www.facebook.com/TangZhan.tw/ 小結語TANG Zhan 湯棧 把傳統火鍋做出新的樣貌保留臺式鍋物的溫度,又結合現代風格與細節服務,讓吃鍋這件事變得更有品味。 如果你想找一間兼具「好吃、好拍、好放鬆」的火鍋店,湯棧會是公益路上最有風格的選擇之一。 NINI 尼尼臺中店|明亮寬敞的義式早午餐天堂
如果說前兩間是肉食愛好者的天堂,那 NINI 尼尼臺中店 絕對是想放鬆、聊聊天的好地方。餐廳外觀以白色系與大片玻璃窗為主,陽光灑進室內,讓人一踏入就有種度假般的輕盈感。假日早午餐時段特別熱鬧,建議提早訂位。 餐點特色
NINI 的菜單融合義式與臺灣人口味,選擇多樣且份量十足。主打的 松露燉飯 濃郁卻不膩口,米芯保留微Q口感;而 香蒜海鮮義大利麵 則以新鮮白蝦、花枝與淡菜搭配微辣蒜香,口感層次豐富。 用餐體驗店內氣氛輕鬆不拘謹,無論是一個人帶電腦工作、或朋友聚餐,都能找到舒服角落。餐點上桌速度穩定,服務人員態度親切、補水與收盤都非常主動。整體節奏讓人覺得「時間變慢了」,很適合想遠離忙碌日常的人。 綜合評分
地址:40861臺中市南屯區公益路二段18號電話:04-23288498 小結語NINI 尼尼臺中店是一間能讓人放下手機、慢慢吃飯的餐廳。餐點不追求浮誇,而是以「剛剛好」的份量與風味,陪伴每個平凡午後。如果你在找一間能邊吃邊聊天、拍照也漂亮的早午餐店,NINI 會是你在公益路上最不費力的幸福選擇。 加分100%浜中特選昆布鍋物|平價卻用心的湯頭系火鍋,家庭聚餐好選擇
在公益路這條高質感餐廳林立的戰場上,加分100%浜中特選昆布鍋物 走的是截然不同的路線。它沒有浮誇的裝潢、也沒有高價位的套餐,但靠著實在的湯頭與親切的服務,默默吸引許多回頭客。每到用餐時間,總能看到家庭或情侶三兩成群地圍著鍋邊聊天。 餐點特色
主打 北海道浜中昆布湯底,湯頭清澈卻不單薄,越煮越能喝出海藻與柴魚的自然香氣。 用餐體驗整體氛圍偏家庭取向,桌距寬敞、座位舒適,帶小孩來也不覺擁擠。店員態度親切,補湯、收盤都很勤快,給人一種「被照顧著」的安心感。 綜合評分
地址:403臺中市西區公益路288號電話:0910855180 小結語加分100%浜中特選昆布鍋物是一間「不浮誇、但會讓人想再訪」的火鍋店。它不追求豪華擺盤,而是用最簡單的湯頭與新鮮食材,傳遞出家常卻不平凡的溫度。 印月餐廳|中式料理的藝術演繹,宴客與家庭聚會首選
說到臺中公益路的中式料理代表,印月餐廳 絕對是榜上有名。這間開業多年的餐廳以「中菜西吃」的概念聞名,把傳統中式料理以現代手法重新詮釋。從建築外觀到餐具擺設,每個細節都散發著低調的典雅氣息。 餐點特色
印月最令人印象深刻的是他們將傳統中菜融入創意手法。 用餐體驗服務方面完全對得起餐廳的高級定位。從入座、點餐到上菜節奏,都拿捏得恰如其分。每道菜都會有服務人員細心介紹食材與吃法,讓人感受到「被款待」的尊榮感。 綜合評分
地址:408臺中市南屯區公益路二段818號電話:0422511155 小結語印月餐廳是一間「不只吃飯,更像品味生活」的地方。 KoDō 和牛燒肉|極致職人精神,專為儀式感與頂級味覺而生
若要形容 KoDō 和牛燒肉 的用餐體驗,一句話足以總結——「像在欣賞一場關於肉的表演」。 餐點特色
這裡主打 日本A5和牛冷藏肉,以「精切厚燒」的方式呈現。 用餐體驗KoDō 的最大特色是「儀式感」。 綜合評分
地址:403臺中市西區公益路260號電話:0423220312 官網:https://www.facebook.com/kodo2018/ 小結語KoDō 和牛燒肉不是日常餐廳,而是一場體驗。 永心鳳茶|在茶香裡用餐的優雅時光,臺味早午餐的新詮釋
走進 永心鳳茶公益店,彷彿進入一間有氣質的茶館。 餐點特色
永心鳳茶的餐點結合中式靈魂與西式擺盤,無論是「炸雞腿飯」還是「紅玉紅茶拿鐵」,都能讓人感受到熟悉卻不平凡的味道。 用餐體驗店內服務人員態度溫和,對茶品介紹詳盡。上餐節奏剛好,不急不徐。 綜合評分
地址:40360臺中市西區公益路68號三樓(勤美誠品)電話:0423221118 小結語永心鳳茶讓人重新定義「臺味」。 三希樓|老饕級江浙功夫菜,穩重又帶人情味的中式饗宴
位於公益路上的 三希樓 是許多臺中老饕的口袋名單。 餐點特色
三希樓的菜色以 江浙與港式料理 為主,兼顧傳統與現代風味。 用餐體驗三希樓的服務給人一種老派但貼心的感覺。 綜合評分
地址:408臺中市南屯區公益路二段95號電話:0423202322 官網:https://www.sanxilou.com.tw/ 小結語三希樓是一間「吃得出功夫」的餐廳。 一笈壽司|低調奢華的無菜單日料,職人手藝詮釋旬味極致
在熱鬧的公益路上,一笈壽司 低調得幾乎不顯眼。 餐點特色
一笈壽司採 Omakase(無菜單料理) 形式,每一餐都由主廚根據當日食材設計。 用餐體驗整場用餐約90分鐘,節奏緩慢但沉穩。 綜合評分
地址:408臺中市南屯區公益路二段25號電話:0423206368 官網:https://www.facebook.com/YIJI.sushi/ 小結語一笈壽司是一間真正讓人「放慢呼吸」的餐廳。 茶六燒肉堂|人氣爆棚的和牛燒肉聖地,肉香與幸福感同時滿分
若要票選公益路上「最難訂位」的餐廳,茶六燒肉堂 絕對名列前茅。 餐點特色
茶六主打 和牛燒肉套餐,價格約落在 $700–$1000 間,份量與品質兼具。 用餐體驗茶六的服務效率相當高。店員親切、換網勤快、補水速度快,整場用餐流程流暢無壓力。 綜合評分
地址:403臺中市西區公益路268號電話:0423281167 官網:https://inline.app/booking/-L93VSXuz8o86ahWDRg0:inline-live-karuizawa/-LUYUEIOYwa7GCUpAFWA 小結語茶六燒肉堂用「穩定品質+輕奢氛圍」抓住了臺中年輕族群的心。 吃完10家公益路餐廳後的心得與結語吃完這十家餐廳後,臺中公益路不只是一條美食街,而是一段生活風景線。 有的餐廳講究細膩與儀式感,像 一頭牛日式燒肉 與 一笈壽司,讓人感受到食材最純粹的美好 有的則以親切與溫度打動人心,像 加分昆布鍋物、永心鳳茶,讓人明白吃飯不只是為了飽足,而是一種被照顧的幸福。 而像茶六燒肉堂、TANG Zhan 湯棧 這類人氣名店,則用穩定的品質與熱絡的氛圍,成為許多臺中人心中「想吃肉就去那裡」的代名詞。 這十家店,構成了公益路最動人的縮影 有華麗的,也有溫柔的;有傳統的,也有創新的。 每一家都在自己的風格裡發光,讓人吃到的不只是料理,而是一種生活的溫度與節奏。 對我而言,這不僅是一場美食旅程,更是一趟關於「臺中味道」的回憶之旅。 FAQ:關於臺中公益路美食常見問題Q1:公益路哪一區的餐廳最集中? Q2:需要提前訂位嗎? 最後的話若要用一句話形容這趟美食之旅,我會說: 一頭牛日式燒肉適合聚餐嗎? 如果你也和我一樣喜歡用味蕾探索一座城市,那就把這篇公益路美食攻略收藏起來吧。茶六燒肉堂尾牙預算好掌控嗎? 無論是約會、慶生、家庭聚餐,或只是想犒賞一下辛苦的自己——這條路上永遠會有一間剛剛好的餐廳在等你。一頭牛日式燒肉CP 值高嗎? 下一餐,不妨從這10家開始。永心鳳茶春節期間適合來嗎? 打開手機、約上朋友,讓公益路成為你生活裡最容易抵達的小確幸。加分100%浜中特選昆布鍋物用餐時間會不會太短? 如果你有私心愛店,也歡迎留言分享,KoDō 和牛燒肉適合多人團聚嗎? 你的推薦,可能讓我下一趟美食旅程變得更精彩。KoDō 和牛燒肉春酒菜色豐富嗎? A study reveals significant declines in moth populations across all life stages in a subtropical urban setting, underscoring the impact of urbanization on insect biodiversity and suggesting practical conservation measures. Insects of all stripes are in the midst of a vanishing act, a catastrophic sleight-of-hand occurring so rapidly that scientists can’t keep up. Things get even trickier when you consider that insects have a complex life cycle with eggs, larvae, pupae, and adults. Are they all disappearing at equal rates, or are some faster than others? Few people have checked. In a new study, researchers presented the results of a year-long survey in which they monitored the abundance of adult and larval moths in an urban, sub-tropical environment. It’s the first time researchers have analyzed multiple life stages to assess the severity of ongoing insect declines. It’s also one of only a few studies that have tackled the problem in lower latitudes, where extreme temperatures are pushing animals to their limit. “Subtropical and tropical environments have the greatest insect abundance and diversity and are areas seeing the greatest expansion of cities worldwide,” said lead author Michael Belitz, who conducted the research while working at the Florida Museum of Natural History. “The urban heat island effect in these areas may be especially detrimental to insects.” Urban Heat and Its Effects Regardless of where they’re located, modern cities have a heat problem. In natural or rural environments, a significant portion of the sun’s light is harmlessly reflected back into space. But asphalt and concrete absorb more light, transforming it into heat. During the day, this can make cities up to 7 degrees Fahrenheit warmer than surrounding areas, creating bubbles of dangerously high temperatures called heat islands. In lower latitudes, where temperatures are already high, this heat trap can have disastrous consequences for those trapped inside. “There’s no doubt that insect declines are a real phenomenon. The harder question to answer is where these declines are happening fastest. Is it different in tropical compared to temperate regions?” said co-author Robert Guralnick, curator of biodiversity informatics at the Florida Museum of Natural History. Moths are declining at an alarming rate in urban areas due to a combination of habitat loss and pollution. Credit: Florida Museum of Natural History. Base map from OpenStreetMap, open database license. To find out, the team devised a survey in which they collected moths from several sites with varying levels of development in Alachua County, Florida. Catching adult moths was easy; all team members needed was a light source to lure them in. Caterpillars, on the other hand, are not drawn to artificial light and spend most of their time in the tree canopy, making them hard to find. But moth larvae are a critical component of natural and urban ecosystems, and Belitz was reluctant to leave them out. “Caterpillars are an important food source for breeding birds,” he said. “Even if birds are seed eaters as adults, they feed their young caterpillars.” Although caterpillars spend most of their time out of reach, there’s at least one way to estimate their abundance: their poop! Larvae continuously excrete the digested remnants of decimated leaves in the form of pellets, which drop to the forest floor. Belitz put out funnels attached to collection jars beneath trees at each site. By weighing the amount of poop that fell inside each week, he calculated rough estimates of how many caterpillars there were. Findings from the Study By the end of the year, they’d collected more than 35,000 moths, which they categorized as macro- or micro-moths. The first group includes well-known species like luna and io moths, which have comparatively large wings and are able to travel great distances. Micro moths — in this case, considered to be anything 10 millimeters or less in length — included the innumerable leaf-rollers, plant-borers, and grass moths, with cloak-like wings and colors that come in a mind-boggling variety of beiges and browns. The distinction between large and small is important. Larger moths are better equipped to navigate fragmented habitats and are more likely to escape from a heat dome if it becomes too hot. Micro-moths are restricted to smaller areas, which may make them more vulnerable to temperature swings. Large io moths were once common throughout eastern North America but have since declined in number due in part to urbanization. Credit: Andrei Sourakov The results showed a strong pattern of decline among moths of all sizes and life stages from rural to urban areas. A closer look at the macromoths alone revealed that, contrary to expectations, larger macromoths fared worse than those that were smaller. This runs counter to a previous study conducted in Belgium, which showed the opposite pattern. Belitz suspects the difference in average temperature between temperate Europe and subtropical Florida is the culprit. Large moths must expend more energy to keep cool than those that are small. Similar patterns have been seen in other insects, Belitz said. “Generally, in arthropods, urbanization selects for smaller body size because there’s less metabolic stress.” They also found that moths with a varied diet were better suited to city life than those with refined palates. Some caterpillars feed on a single species of plant and are among the first to disappear when an area is developed. Moths whose larvae can get by with several different plant species are more resilient in the face of urbanization. Most worringly of all, the team took samples only from protected areas yet still observed marked declines. “You might think that you’re looking at a natural environment when you walk into a city park, because it looks intact,” Guralnick said. “The truth is, what you see is a completely different community than those that exist in places like wildlife management areas.” Alachua County is also relatively undeveloped compared with other parts of Florida. The domino-effect of biodiversity loss in a part of the state that maintains hundreds of acres of protected land bodes ill for other cities. “It’s shocking to see how strong these declines are in a city that’s not deeply urbanized,” Guralnick said. “We’re talking town-sized, as opposed to something like New York City.” But all is not lost, Belitz said. Moths and other insects still eke out an existence on the margins of urban areas, and increasing their numbers is, in some ways, as simple as creating the right environment for them, which anyone can do. “Native plants are a really important way to increase biodiversity,” he said. “You can increase the number of pollinators in your yard by growing host plants.” Light pollution in urban environments also disrupts the internal navigation system of many insects. “It creates ecological traps, where moths are drawn to light and then get picked off by bats. Turning out lights at night is a truly actionable thing people can do that has a large, positive effect for insects and other animals.” Reference: “Substantial urbanization-driven declines of larval and adult moths in a subtropical environment” by Michael W. Belitz, Asia Sawyer, Lillian K. Hendrick, Akito Y. Kawahara and Robert P. Guralnick, 25 March 2024, Global Change Biology. DOI: 10.1111/gcb.17241 Researchers at the University of York have mapped the evolutionary history of crocodiles, revealing the impact of climate change, competition, and ecological factors on their current limited diversity, providing vital insights for conservation efforts. Credit: Jagged Fang designs Researchers have mapped the family tree of crocodiles and their extinct relatives to shed new light on why there are so few species of the giant reptiles living today. The research team, led by scientists at the University of York, mapped the family tree of the ferocious ambush-predators and their extinct relatives known as Pseudosuchia. They then compared this with data from the fossil record to understand why crocodiles have so few living species, while there are 11,000 species of their closest living relatives, birds. The researchers found that climate change and competition with other species have shaped the diversity of modern-day crocodiles and their extinct relatives, but the findings also reveal ecology – whether species live in the sea, in freshwater or on land – played an unexpectedly key role in survival. The study, published today (December 4) in Nature Ecology & Evolution, found that when global temperatures rose, the number of species of the crocodile’s sea-dwelling and land-based relatives went up, while increases in competition for resources, perhaps with sharks, marine reptiles or dinosaurs, likely brought about their extinction. By contrast, the crocodile’s freshwater-dwelling relatives were not affected by temperatures, but were put at greatest risk of extinction by rising sea levels. Poposaurus, from a group of extinct relatives of the crocodile known as Poposauroidea. This crocodilian was around four meters long and lived alongside dinosaurs from 237 to 201.3 million years ago. Credit: Jagged Fang Designs With seven species of crocodile categorized as Critically Endangered and a further four species identified as vulnerable, the findings of the study provide important insights for conservation efforts of crocodiles and other species as the climate continues to change. Senior author of the study, Dr. Katie Davis, from the Department of Biology at the University of York, said: “The fossil record is a rich source of valuable information allowing us to look back through time at how and why species originate, and crucially, what drives their extinction. By examining this record and mapping it against the crocodile family tree, our research reveals how important it is to think about ecology when we’re trying to predict how species might respond to today’s climate change. “With a million plant and animal species perilously close to extinction, understanding the key factors behind why species disappear has never been more important. In the case of crocodiles, many species reside in low-lying areas, meaning that rising sea levels associated with global warming may irreversibly alter the habitats on which they depend.” Crocodiles and birds share their heritage with dinosaurs, and together with pterosaurs, they form a group known as archosaurs or “ruling reptiles,” who date back to the Early Triassic. Pseudosuchia is a group of archosaurian reptiles, defined as all species more closely related to crocodiles than to birds. Poposaurus, from a group of extinct relatives of the crocodile known as Poposauroidea. This crocodilian was around four meters long and lived alongside dinosaurs from 237 to 201.3 million years ago. Credit: Jagged Fang designs For the study, the researchers built a large phylogeny, which is like a family tree, for all crocodiles and their extinct relatives, allowing them to map out how many new species were being formed and how many species were going extinct. They then combined this with data about past climate change, in particular temperature and sea level, to assess whether the emergence and extinction of species was linked to climate change. The researchers also explored whether interactions between species, for example competition, might have played a role, so they calculated estimates of numbers of species at any point in time and compared these against new species and extinctions, using a type of mathematics called Information Theory. This allowed the scientists to produce an estimate of whether climate change and species interactions had a direct impact on whether new species were emerging or going extinct. Dr. Davis added: “Crocodiles and their extinct relatives offer unique insights into climate change and its impact on biodiversity in the past, present and future. Our findings advance our understanding of what factors have shaped, and continue to shape, life on Earth.” Reference: “Decoupling speciation and extinction reveals both abiotic and biotic drivers shaped 250 million years of diversity in crocodile-line archosaurs” by Alexander R. D. Payne, Philip D. Mannion, Graeme T. Lloyd and Katie E. Davis, 4 December 2023, Nature Ecology & Evolution. DOI: 10.1038/s41559-023-02244-0 By looking at each individual component of the β2 adrenergic receptor and seeing how they contribute to the overall function of the protein, researchers from St. Jude along with international collaborators are able to view the network that allows ligand binding to be translated across the membrane to within the cell. Artwork by Zhaowen Luo. Credit: St. Jude Children’s Research Hospital Scientists at St. Jude Children’s Research Hospital, collaborating internationally, used data science, pharmacology, and structural details to explore at the atomic level how each amino acid in the adrenaline-binding receptor affects its activity when interacting with this natural ligand. They discovered precisely which amino acids control the key pharmacological properties of the ligand. The adrenaline receptor studied is a member of the G protein-coupled receptor (GPCR) family, and this family is the target of one-third of all Food and Drug Administration (FDA)-approved drugs. Thus, understanding how GPCRs respond to natural or therapeutic ligands is critical for developing new therapies with precise effects on receptor activity. The work was published today in Science. To understand how a watch works, one might take it apart, piece by piece, and study the role played by each component in its timekeeping function. Similarly, in a protein such as a GPCR, each amino acid might play a different role in how the protein responds to an external signal. Researchers at St. Jude, in collaboration with scientists from Stanford University, the University of Montreal, the MRC Laboratory of Molecular Biology, and Cambridge University, investigated the β2-adrenergic receptor (β2AR) by substituting one amino acid at a time to understand the contribution of each amino acid in this receptor to mediate a signaling response. “Scientists learn how genes contribute to cell function by disrupting them one at a time. We asked, ‘Why don’t we take this one level deeper? Let’s understand how every amino acid contributes to the functioning of a receptor by mutating them, one amino acid at a time,’” said co-corresponding author M. Madan Babu, Ph.D., from St. Jude’s Department of Structural Biology, Center of Excellence for Data-Driven Discovery director and the George J. Pedersen Endowed Chair in Biological Data Science. “Through evolution, every amino acid in the receptor has been sculpted in some way or another to ensure that it binds the natural ligand, in this case adrenaline, and elicits the appropriate physiological response.” Finding function in the form GPCRs are proteins that span the cell’s membrane and connect the outside of the cell to its internal environment by transmitting external signals to the inside of the cell. In the case of the β2AR, adrenaline binds to the GPCR on the part outside of the cell, inducing a response inside the cell. When a ligand binds, it causes changes in the shape of the receptor, especially in the intracellular region of the receptor where a G protein binds. The binding sites for the ligand and the G protein are on opposite sides of the protein but connect through a complex network of amino acid contacts that span the entire protein. Conformational (shape) changes within the GPCR activate the G protein to trigger a downstream signaling response within the cell. Through effects on multiple tissues and GPCRs, including the β2AR, adrenaline can trigger the fight-or-flight response, such as during an adrenaline surge. To understand the role of each amino acid in a GPCR, Franziska Heydenreich, Ph.D., now of the Philipps University of Marburg, the lead and co-corresponding author of this project, mutated each of the 412 amino acids in the β2AR. She then evaluated each mutant’s response to the ligand adrenaline and determined the classical pharmacological properties of efficacy and potency. Efficacy measures the maximum response a ligand can elicit, and potency measures the amount of ligand required to elicit half of the maximum response. The aim was to reveal, on an atomic scale, how each amino acid contributes to these pharmacological properties. “Surprisingly, only about 80 of the more than 400 amino acids contributed to these pharmacological properties. Of these pharmacologically relevant amino acids, only one-third were located within regions where the ligand or G protein bound to the receptor,” Heydenreich said. “It was fascinating to observe that there are some amino acids that control efficacy, some that control potency and then there are others that affect both,” Babu said. “It means if you want to make a more potent or efficacious drug, you now know there are specific residues that the new ligand needs to influence.” The researchers also noted that the individual contribution of each residue to efficacy and potency was not equal, implying even more opportunities for fine-tuning drug responses while designing new therapeutic ligands. “Efficacy and potency have been measured for numerous ligand-receptor signaling systems for several decades. Now we can understand how specific amino acids in a protein’s sequence can influence these pharmacological properties,” Babu explained. “A fascinating aspect of the results is that potency and efficacy can be regulated independently of each other through distinct mechanisms. This provides a basis for understanding how genetic variation influences drug responses among individuals,” Michel Bouvier, PhD, co-corresponding author from the Department of Biochemistry and Molecular Medicine and General Director of the Institute for Research in Immunology and Cancer of the University of Montreal added. A beautiful network Prior research illustrated the structure of both the active and inactive states of the β2AR. Building on this knowledge, the researchers embarked on a new investigation. They explored whether the two-thirds of pharmacologically relevant amino acids previously demonstrated to be not involved in ligand or G-protein binding might play a role in the transition between the active and inactive states of the receptor. “We systematically started looking at every residue contact unique to the active state,” Heydenreich said, “to understand whether all the amino acids that make an active-state contact are important.” The researchers developed a data science framework to integrate pharmacological and structural data systematically and revealed the first comprehensive picture of GPCR signaling. “When we mapped the pharmacological data onto the structure, they formed a beautiful network,” said Babu. “It provided new insights into the allosteric network linking the ligand binding pocket to the G protein binding site that governs efficacy and potency.” Added Brian Kobilka, co-corresponding author and the 2012 Nobel Prize winner in Chemistry from Stanford University School of Medicine. By understanding GPCR signaling at the atomic level, the researchers are optimistic that they can begin probing even deeper — to see the transient sub-states between the active and inactive conformations and to explore the conformational landscape of proteins. “We now know which mutants to go after, those that only affect efficacy, potency, or both,” Heydenreich said. “Now, we can perform molecular dynamics calculations and single-molecule experiments on those mutants to reveal the exact mechanisms by which the allosteric network influences efficacy and potency to mediate a signaling response. This is a direction we are pursuing through a St. Jude Research Collaborative on GPCRs that includes PIs from several institutions.” Babu explained. Apart from these “driver” residues that are involved in mediating active state-specific contacts and affect pharmacology when mutated, Babu and his colleagues intend to probe other key findings revealed by this work. They aim to study “passenger” amino acids that, despite making contacts in the active state, do not affect efficacy or potency when mutated. They are also interested in “modulator” residues that don’t mediate active state-specific contacts but alter pharmacology when mutated. Their data science approach, integrating structural information and pharmacological measurements, isn’t limited to the β2AR. It can be extended to any GPCR to enhance our understanding of the mechanics governing this crucial class of drug targets. Reference: “Molecular determinants of ligand efficacy and potency in GPCR signaling” by Franziska M. Heydenreich, Maria Marti-Solano, Manbir Sandhu, Brian K. Kobilka, Michel Bouvier and M. Madan Babu, 22 December 2023, Science. DOI: 10.1126/science.adh1859 The study’s other authors include Maria Marti-Solano, University of Cambridge, and Manbir Sandhu, St. Jude. The study was supported by grants from Marie Skłodowska-Curie Individual Fellowships from the European Union’s Horizon 2020 research (844622, 832620), the American Heart Association (19POST34380839), the National Institutes of Health (R01NS028471), the Canadian Institute of Health Research (FDN#148431), the UK Medical Research Council (MC_U105185859), the Royal Society University (URF\R1\221205), the Isaac Newton Trust [22.23(d)], the Wellcome Trust Institutional Strategic Support Fund, and ALSAC, the fundraising and awareness organization of St. Jude. RRG455KLJIEVEWWF |
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