rewiring of pdz domain-ligand interaction network contributed to eukaryotic evolution重新布线的pdz domain-ligand交互网络导致真核生物进化.pdfVIP

Rewiring of PDZ Domain-Ligand Interaction Network Contributed to Eukaryotic Evolution 1 1 2 1 3 2 4 Jinho Kim , Inhae Kim , Jae-Seong Yang , Young-Eun Shin , Jihye Hwang , Solip Park , Yoon Sup Choi , Sanguk Kim1,2,3* 1 Division of Molecular and Life Science, Pohang University of Science and Technology, Pohang, Korea, 2 School of Interdisciplinary Bioscience and Bioengineering, Pohang University of Science and Technology, Pohang, Korea, 3 Division of ITCE, Pohang University of Science and Technology, Pohang, Korea, 4 Cancer Research Institute, Seoul National University, Seoul, Korea Abstract PDZ domain-mediated interactions have greatly expanded during metazoan evolution, becoming important for controlling signal flow via the assembly of multiple signaling components. The evolutionary history of PDZ domain-mediated interactions has never been explored at the molecular level. It is of great interest to understand how PDZ domain-ligand interactions emerged and how they become rewired during evolution. Here, we constructed the first human PDZ domain- ligand interaction network (PDZNet) together with binding motif sequences and interaction strengths of ligands. PDZNet includes 1,213 interactions between 97 human PDZ proteins and 591 ligands that connect most PDZ protein-mediated interactions (98%) in a large single network via shared ligands. We examined the rewiring of PDZ domain-ligand interactions throughout eukaryotic evolution by tracing changes in the C-terminal binding motif sequences of the PDZ ligands. We found that interaction rewiring by sequence mutation frequently occurred throughout evolution, largely contributing to the growt