6gqe
From Proteopedia
X-ray structure of KH1-2 domain of IMP3
Structural highlights
Function[IF2B3_HUMAN] RNA-binding factor that may recruits 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. Binds to the 3'-UTR of CD44 mRNA and stabilizes it, hence promotes cell adhesion and invadopodia formation in cancer cells. Binds to beta-actin/ACTB and MYC transcripts. Binds to the 5'-UTR of the insulin-like growth factor 2 (IGF2) mRNAs.[1] [2] Publication Abstract from PubMedHow multidomain RNA-binding proteins recognize their specific target sequences, based on a combinatorial code, represents a fundamental unsolved question and has not been studied systematically so far. Here we focus on a prototypical multidomain RNA-binding protein, IMP3 (also called IGF2BP3), which contains six RNA-binding domains (RBDs): four KH and two RRM domains. We establish an integrative systematic strategy, combining single-domain-resolved SELEX-seq, motif-spacing analyses, in vivo iCLIP, functional validation assays, and structural biology. This approach identifies the RNA-binding specificity and RNP topology of IMP3, involving all six RBDs and a cluster of up to five distinct and appropriately spaced CA-rich and GGC-core RNA elements, covering a >100 nucleotide-long target RNA region. Our generally applicable approach explains both specificity and flexibility of IMP3-RNA recognition, allows the prediction of IMP3 targets, and provides a paradigm for the function of multivalent interactions with multidomain RNA-binding proteins in gene regulation. Combinatorial recognition of clustered RNA elements by the multidomain RNA-binding protein IMP3.,Schneider T, Hung LH, Aziz M, Wilmen A, Thaum S, Wagner J, Janowski R, Muller S, Schreiner S, Friedhoff P, Huttelmaier S, Niessing D, Sattler M, Schlundt A, Bindereif A Nat Commun. 2019 May 22;10(1):2266. doi: 10.1038/s41467-019-09769-8. PMID:31118463[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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