Antifungal drug discovery and design is very challenging because of the considerable similarities in genetic features and metabolic pathways between fungi and humans. However, cell wall composition represents a notable point of divergence. Therefore, a research strategy was designed to improve our understanding of the mechanisms for maintaining fungal cell wall integrity, and to identify potential targets for new drugs that modulate the underlying protein-protein interactions in Saccharomyces cerevisiae. This study defines roles for Wsc2p and Wsc3p and their interacting protein partners in the cell wall integrity signaling and cell survival mechanisms that respond to treatments with fluconazole and hydrogen peroxide. By combined genetic and biochemical approaches, we report the discovery of 12 novel protein interactors of Wsc2p and Wsc3p. Of these, Wsc2p interacting partners Gtt1p and Yck2p, have opposing roles in the resistance and sensitivity to fluconazole treatments respectively. The interaction of Wsc2p with Ras2p was confirmed by iMYTH and IP-MS approaches and is shown to play a dominant role in response to oxidative stress induced by hydrogen peroxide. Consistent with an earlier study, Ras2p was also identified as an interacting partner of Wsc1p and Mid2p cell wall integrity signaling proteins. Collectively, this study expands the interaction networks of the mechanosensory proteins of the Cell Wall Integrity pathway.

由于真菌和人类之间的遗传特征和代谢途径具有相当大的相似性，抗真菌药物的发现和设计非常具有挑战性。然而，细胞壁组成代表了一个显着的分歧点。因此，一项研究策略旨在提高我们对维持真菌细胞壁完整性机制的理解，并确定调节酿酒酵母中潜在蛋白质-蛋白质相互作用的新药的潜在靶点。本研究定义了Wsc2p和Wsc3p以及它们在细胞壁完整性信号传导和细胞存活机制中相互作用的蛋白质伙伴，这些机制对氟康唑和过氧化氢的治疗有反应。通过结合遗传和生化方法，我们报告了 12 种新型蛋白质相互作用物的发现。Wsc2p和Wsc3p. 这些，Wsc2p互动伙伴Gtt1p和Yck2p，分别在对氟康唑治疗的耐药性和敏感性方面具有相反的作用。的相互作用Wsc2p和拉斯2p通过 iMYTH 和 IP-MS 方法得到证实，并显示在过氧化氢诱导的氧化应激反应中起主导作用。与较早的研究一致，拉斯2p也被确定为合作伙伴Wsc1p和Mid2p细胞壁完整性信号蛋白。总的来说，这项研究扩展了细胞壁完整性途径的机械感觉蛋白的相互作用网络。