本實驗室研究重點是細胞週期進程中的蛋白質交互作用及訊息傳遞,尤其是癌細胞和病毒感染方面。我們在INK4、Ki67、CHK2蛋白質的結構和功能研究中,為一些癌症的機制研究提供了新契機。此外,我們研究人類(例如MDC1)和酵母(Rad53及Dun1)FHA domain傳達的蛋白質和磷蛋白之間的反應訊息路徑及結構。本實驗室另一個計畫著重在DNA聚合酶催化反應機制和生化功能,包括人類DNA聚合酶beta及lambda和非洲豬瘟病毒(African swine fever virus, ASFV)所帶有的DNA聚合酶X。研究此酵素特性使我們更進一步了解DNA層次的損傷反應和修復。最近,在台灣蛋白質計劃的支持下,他一直積極從事使用時間分辨的系列飛秒X射線晶體學研究DNA光解酶的機制,以及將cryo-EM應用於酶學的反應機理研究。
An ATP-sensitive phosphoketolase regulates carbon fixation in cyanobacteria.
Lu KJ, Chang CW, Wang CH, Chen FY, Huang IY, Huang PH, Yang CH, Wu HY, Wu WJ, Hsu KC, Ho MC, Tsai MD, Liao JC
Nature Metabolism (2023)
Enzymology and Dynamics by Cryogenic Electron Microscopy.
Tsai MD, Wu WJ, Ho MC
Annual Review of Biophysics (2022)
Preparation of High-Temperature Sample Grids for Cryo-EM.
Chang YC, Chen CY, Tsai MD
Journal of Visualized Experiments (2021)
Identification of fidelity-governing factors in human recombinases DMC1 and RAD51 from cryo-EM structures.
Luo SC, Yeh HY, Lan WH, Wu YM, Yang CH, Chang HY, Su GC, Lee CY, Wu WJ, Li HW, Ho MC, Chi P, Tsai MD
Nature Communications (2021)
Temperature-Resolved Cryo-EM Uncovers Structural Bases of Temperature-Dependent Enzyme Functions.
Chen CY, Chang YC, Lin BL, Huang CH, Tsai MD
Journal of the American Chemical Society (2019)
Human DNA Polymerase μ Can Use a Noncanonical Mechanism for Multiple Mn2+-Mediated Functions.
Chang YK, Huang YP, Liu XX, Ko TP, Bessho Y, Kawano Y, Maestre-Reyna M, Wu WJ, Tsai MD
Journal of the American Chemical Society (2019)
Use of Cryo-EM To Uncover Structural Bases of pH Effect and Cofactor Bispecificity of Ketol-Acid Reductoisomerase.
Chen CY, Chang YC, Lin BL, Lin KF, Huang CH, Hsieh DL, Ko TP, Tsai MD
Journal of the American Chemical Society (2019)