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Cryo-EM structure of ASK1 reveals mechanistic basis of its redox-dependent activation

Mgr. Dalibor Košek, Ph.D., Laboratory of Structural biology of signaling proteins, IPHYS (detached workplace BIOCEV)

ASK1 (apoptosis signal-regulating kinase 1) is a member of MAP3K protein family, which directs the cell towards inflammation or apoptosis through p38 or JNK signaling pathway. ASK1 dysregulation has been associated with cardiovascular, tumor and neurodegenerative disorders and ASK1, thus, represents a prospective target for therapeutic intervention. ASK1 regulation involves both oligomerization and interaction with multiple binding partners, however, key aspects of the activation remains unclear. To better understand the principle of ASK1 activation, we investigated the structure and oligomeric behavior of N-terminal part of ASK1. Our results provide first insight into the structural organization of the complex and suggest how potential binding partners could affect ASK1 functions.


Dalibor Košek received his Ph.D. in Physical Chemistry from the Charles University. Then he joined the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK/NIH, MD U.S.A.) as a visiting fellow where he received extensive postdoctoral training in structural biology. Among his major achievements so far are the structural characterizations of several eukaryotic and prokaryotic DNA transposition mechanisms, which have opened the way to their potential future applications in biotechnology and medicine. In 2021, Dalibor Košek joined the Laboratory of Structural Biology of Signaling Proteins at IPHYS, detached workplace BIOCEV, where he initiated cryo-EM studies of several complexes important for intracellular signaling.

IPHYS contact person: Dalibor Košek,, Veronika Obšilová,