6GQE

X-ray structure of KH1-2 domain of IMP3

Summary for 6GQE

• Entry DOI: 10.2210/pdb6gqe/pdb
• Descriptor: Insulin-like growth factor 2 mRNA-binding protein 3 (2 entities in total)
• Functional Keywords: multidomain-rna binding protein, insulin-like growth factor 2, mrna binding protein 3 (imp3), mrna-protein interactions, rna binding protein
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 1
• Total formula weight: 18626.42

Authors

Janowski, R.,Schlundt, A.,Sattler, M.,Niessing, D. (deposition date: 2018-06-07, release date: 2019-04-24, Last modification date: 2024-01-17)

Primary citation

Schneider, T.,Hung, L.H.,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.
Combinatorial recognition of clustered RNA elements by the multidomain RNA-binding protein IMP3.
Nat Commun, 10:2266-2266, 2019

PubMed Abstract: How 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.

PubMed: 31118463
DOI: 10.1038/s41467-019-09769-8

Experimental method

X-RAY DIFFRACTION (2.15 Å)