biostudies-literatureSu CNational Natural Science Foundation of China107694https://www.ebi.ac.uk/biostudies/studies/S-EPMC11480233biostudies-literatureUnknown300(10)The canonical Wnt signaling pathway plays crucial roles in cell fate decisions as well as in pathogenesis of various diseases. Previously, we reported Caprin-2 as a new regulator of canonical Wnt signaling through a mechanism of facilitating LRP5/6 phosphorylation. Here, we resolved the crystal structure of the N-terminal homologous region 1 (HR1) domain of human Caprin-2. HR1 domain is so far only observed in Caprin-2 and its homologous protein Caprin-1, and the function of this domain remains largely mysterious. Here, the structure showed that HR1 domain of human Caprin-2 forms a homo-dimer and exhibits an overall structure roughly resembling the appearance of a pair of scissors. Moreover, we found that residues R200 and R201, which located at a basic cluster within the N-terminal "bladeThe Journal of biological chemistryStructural insights into the Caprin-2 HR1 domain in canonical Wnt signaling.PMC114802333110053231530094Su CMiao HZhong YLuo HShi ZLi LXie SZhou ZLi YLi ZJia YSong XZhao JfalseStructural insights into the Caprin-2 HR1 domain in canonical Wnt signaling.The canonical Wnt signaling pathway plays crucial roles in cell fate decisions as well as in pathogenesis of various diseases. Previously, we reported Caprin-2 as a new regulator of canonical Wnt signaling through a mechanism of facilitating LRP5/6 phosphorylation. Here, we resolved the crystal structure of the N-terminal homologous region 1 (HR1) domain of human Caprin-2. HR1 domain is so far only observed in Caprin-2 and its homologous protein Caprin-1, and the function of this domain remains largely mysterious. Here, the structure showed that HR1 domain of human Caprin-2 forms a homo-dimer and exhibits an overall structure roughly resembling the appearance of a pair of scissors. Moreover, we found that residues R200 and R201, which located at a basic cluster within the N-terminal "blade2024-01-01T00:00:00Z2024 Oct2026-06-01T09:54:06.418Z2025-04-04T01:25:56.386ZS-EPMC114802333915981610.1016/j.jbc.2024.107694