Integrative solution structure of PTBP1-IRES complex reveals strong compaction and ordering with residual conformational flexibility
Abstract
RNA-binding proteins (RBPs) are crucial regulators of gene expression, often composed of defined domains interspersed with flexible, intrinsically disordered regions. Determining the structure of ribonucleoprotein (RNP) complexes involving such RBPs necessitates integrative structural modeling due to their lack of a single stable state. In this study, we integrate magnetic resonance, mass spectrometry, and small-angle scattering data to determine the solution structure of the polypyrimidine-tract binding protein 1 (PTBP1/hnRNP I) bound to an RNA fragment from the internal ribosome entry site (IRES) of the encephalomyocarditis virus (EMCV). This binding, essential for enhancing the translation of viral RNA, leads to a complex structure that demonstrates RNA and protein compaction, while maintaining pronounced conformational flexibility. Acting as an RNA chaperone, PTBP1 orchestrates the IRES RNA into a few distinct conformations, exposing the RNA stems outward. This conformational diversity is likely common among RNP structures and functionally important. Our approach enables atomic-level characterization of heterogeneous RNP structures. Show more
Permanent link
https://doi.org/10.3929/ethz-b-000637820Publication status
publishedExternal links
Journal / series
Nature CommunicationsVolume
Pages / Article No.
Publisher
NatureOrganisational unit
03810 - Jeschke, Gunnar / Jeschke, Gunnar
03857 - Mezzenga, Raffaele / Mezzenga, Raffaele
03591 - Allain, Frédéric / Allain, Frédéric
03927 - Picotti, Paola / Picotti, Paola
Funding
149921 - NMR structure determination of protein-RNA complexes involved in pre-mRNA splicing and translation regulation (SNF)
170130 - NMR structure determination of protein-RNA complexes involved in pre-mRNA splicing and translation regulation (SNF)
ETH-24 16-2 - A new technology for the structural analysis of protein-RNA interactions at single residue resolution and its application to understand pre-miRNA processing in vitro and in vivo. (ETHZ)
170976 - Role of Disordered Regions in RNA-Binding Proteins for Function and Pathology (SNF)
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