7VKL

Crystal structure of MmIMP3-KH12 in complex with zipcode RNA

Summary for 7VKL

• Entry DOI: 10.2210/pdb7vkl/pdb
• Descriptor: Insulin-like growth factor 2 mRNA-binding protein 3, RNA (8-mer) (3 entities in total)
• Functional Keywords: imp3, igf2bp, zipcode, rna binding, m6a, rna binding protein, rna binding protein-rna complex, rna binding protein/rna
• Biological source: Mus musculus (Mouse); More
• Total number of polymer chains: 2
• Total formula weight: 20852.71

Authors

Li, X.J.,Wu, B.X. (deposition date: 2021-09-30, release date: 2022-10-05, Last modification date: 2025-03-05)

Primary citation

Li, X.,Guo, W.,Wen, Y.,Meng, C.,Zhang, Q.,Chen, H.,Zhao, X.,Wu, B.
Structural basis for the RNA binding properties of mouse IGF2BP3.
Structure, 2025

PubMed Abstract: IGF2BP family proteins (IGF2BPs) contain six tandem RNA-binding domains (RBDs), resulting in highly complex RNA binding properties. Dissecting how IGF2BPs recognize their RNA targets is essential for understanding their regulatory roles in gene expression. Here, we have determined the crystal structures of mouse IGF2BP3 constructs complexed with different RNA substrates. Our structures reveal that the IGF2BP3-RRM12 domains can recognize CA-rich elements up to 5-nt in length, mainly through RRM1. We also captured the antiparallel RNA-binding mode of the IGF2BP3-KH12 domains, with five nucleotides bound by KH1 and two nucleotides bound by KH2. Furthermore, our structural and biochemical studies suggest that the IGF2BP3-KH12 domains could recognize the "zipcode" RNA element within the β-actin mRNA. Finally, we analyzed the similarities and differences of the RNA-binding properties between the KH12 and KH34. Our studies provide structural insights into RNA target recognition by mouse IGF2BP3.

PubMed: 39986276
DOI: 10.1016/j.str.2025.01.022

Experimental method

X-RAY DIFFRACTION (1.95 Å)