Article info Vol. 3  No. 1   pp.  55 ~ 60
Title Structural analysis of mouse GSK3β fused with the LRP6 peptide
Authors Kuglae Kim1, Jin-Sik Kim2, Jeong Seok Cha1, Hyun-Soo Cho1* and Nam-Chul Ha2*
Institutions 1Department of Systems Biology, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749, Korea, 2Department of Agricultural Biotechnology, Center for Food Safety and Toxicology, Center for Food and Bioconvergence, Research Institute for Agricultural and Life Sciences, Seoul National University, Seoul 151-921, Korea. *Correspondence: hanc210@snu.ac.kr (N. C. Ha) or hscho8@yonsei.ac.kr (H. S. Cho)
Abstract Glycogen synthase kinase-3β (GSK3β) is a highly conserved kinase that functions as a key regulator of many cellular signalling pathways. Unlike other kinases, GSK3β transduces signalling via inhibition by upstream kinases or factors. In the Wnt/β-catenin signalling pathway, the Wnt coreceptor LRP6/5 serves as a direct inhibitor of GSK3β when the PPPSP motif in LRP6/5 is phosphorylated upon Wnt activation. We constructed a chimeric protein composed of the PPPSP motif and the mouse GSK3β to determine the crystal structure of GSK3β in complex with the phosphorylated LRP6 peptide. The crystal structure of the chimeric protein was determined at a 2.6 Å resolution using protein expressed in insect cells. Our GSK3β structure was compared with other previously determined structures. The dimeric assembly provided implications for the functional significance of the kinase dimer. The phospho-Ser/Thr binding pocket contained a malonate molecule derived from the crystallization solution. Our findings will increase our understanding of the structure of this multifunctional kinase, which is a potential therapeutic target for diabetes and neurological disorders.