8K9D

Structure of human Caprin-2 HR1 domain

Summary for 8K9D

• Entry DOI: 10.2210/pdb8k9d/pdb
• Descriptor: Caprin-2 (1 entity in total)
• Functional Keywords: wnt signaling, homodimer, signaling protein
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 1
• Total formula weight: 30547.91

Authors

Song, X.M. (deposition date: 2023-07-31, release date: 2024-08-21, Last modification date: 2025-03-05)

Primary citation

Su, C.,Zhong, Y.,Zhou, Z.,Li, Y.,Jia, Y.,Xie, S.,Zhao, J.,Miao, H.,Luo, H.,Li, Z.,Shi, Z.,Li, L.,Song, X.
Structural insights into the Caprin-2 HR1 domain in canonical Wnt signaling.
J.Biol.Chem., 300:107694-107694, 2024

PubMed Abstract: 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 "blades" region, are critical for Caprin-2's localization to the plasma membrane. In line with this, mutations targeting these two residues decrease Caprin-2's activity in the canonical Wnt signaling. Overall, we characterized a previously unknown "scissors"-like structure of the full-length HR1 domain and revealed its function in mediating Caprin-2's localization to the plasma membrane.

PubMed: 39159816
DOI: 10.1016/j.jbc.2024.107694

Experimental method

X-RAY DIFFRACTION (3.3 Å)