Download MendeleyIMP1 KH1 and KH2 domains create a structural platform with unique RNA recognition and re-modelling properties.
Dagil, R., Ball, N.J., Ogrodowicz, R.W., Hobor, F., Purkiss, A.G., Kelly, G., Martin, S.R., Taylor, I.A., Ramos, A.(2019) Nucleic Acids Res 47: 4334-4348
- PubMed: 30864660
- DOI: https://doi.org/10.1093/nar/gkz136
- Primary Citation of Related Structures:
6QEY - PubMed Abstract:
IGF2 mRNA-binding protein 1 (IMP1) is a key regulator of messenger RNA (mRNA) metabolism and transport in organismal development and, in cancer, its mis-regulation is an important component of tumour metastasis. IMP1 function relies on the recognition of a diverse set of mRNA targets that is mediated by the combinatorial action of multiple RNA-binding domains. Here, we dissect the structure and RNA-binding properties of two key RNA-binding domains of IMP1, KH1 and KH2, and we build a kinetic model for the recognition of RNA targets. Our data and model explain how the two domains are organized as an intermolecular pseudo-dimer and that the important role they play in mRNA target recognition is underpinned by the high RNA-binding affinity and fast kinetics of this KH1KH2-RNA recognition unit. Importantly, the high-affinity RNA-binding by KH1KH2 is achieved by an inter-domain coupling 50-fold stronger than that existing in a second pseudo-dimer in the protein, KH3KH4. The presence of this strong coupling supports a role of RNA re-modelling in IMP1 recognition of known cancer targets.
Organizational Affiliation:
Research Department of Structural and Molecular Biology, University College London, Darwin Building, Gower Street, London WC1E 6XA, UK.
