7vkl

From Proteopedia

Crystal structure of MmIMP3-KH12 in complex with zipcode RNA

Structural highlights

7vkl is a 2 chain structure with sequence from Mus musculus and Synthetic construct. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.95Å
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

IF2B3_MOUSE RNA-binding factor that may recruit target transcripts to cytoplasmic protein-RNA complexes (mRNPs). This transcript 'caging' into mRNPs allows mRNA transport and transient storage. It also modulates the rate and location at which target transcripts encounter the translational apparatus and shields them from endonuclease attacks or microRNA-mediated degradation. Preferentially binds to N6-methyladenosine (m6A)-containing mRNAs and increases their stability (By similarity). Binds to the 3'-UTR of CD44 mRNA and stabilizes it, hence promotes cell adhesion and invadopodia formation (By similarity). Binds to beta-actin/ACTB and MYC transcripts (By similarity). Increases MYC mRNA stability by binding to the coding region instability determinant (CRD) and binding is enhanced by m6A-modification of the CRD (By similarity). Binds to the 5'-UTR of the insulin-like growth factor 2 (IGF2) mRNAs.[UniProtKB:O00425]^[1]

Publication Abstract from PubMed

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 beta-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.

Structural basis for the RNA binding properties of mouse IGF2BP3.,Li X, Guo W, Wen Y, Meng C, Zhang Q, Chen H, Zhao X, Wu B Structure. 2025 Feb 12:S0969-2126(25)00022-X. doi: 10.1016/j.str.2025.01.022. PMID:39986276^[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Liao B, Hu Y, Herrick DJ, Brewer G. The RNA-binding protein IMP-3 is a translational activator of insulin-like growth factor II leader-3 mRNA during proliferation of human K562 leukemia cells. J Biol Chem. 2005 May 6;280(18):18517-24. Epub 2005 Mar 7. PMID:15753088 doi:http://dx.doi.org/M500270200
↑ 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 Feb 12:S0969-2126(25)00022-X. PMID:39986276 doi:10.1016/j.str.2025.01.022