2MQN

Structural Investigation of hnRNP L

Summary for 2MQN

• Entry DOI: 10.2210/pdb2mqn/pdb
• Related: 2MQL 2MQM 2MQO 2MQP 2MQQ
• NMR Information: BMRB: 25040
• Descriptor: Heterogenous nuclear ribonucleoprotein L (1 entity in total)
• Functional Keywords: protein, rrm, rna binding protein
• Biological source: Rattus norvegicus (rat)
• Total number of polymer chains: 1
• Total formula weight: 24256.36

Authors

Blatter, M.,Allain, F. (deposition date: 2014-06-24, release date: 2015-05-06, Last modification date: 2024-05-15)

Primary citation

Blatter, M.,Dunin-Horkawicz, S.,Grishina, I.,Maris, C.,Thore, S.,Maier, T.,Bindereif, A.,Bujnicki, J.M.,Allain, F.H.
The Signature of the Five-Stranded vRRM Fold Defined by Functional, Structural and Computational Analysis of the hnRNP L Protein.
J.Mol.Biol., 427:3001-3022, 2015

PubMed Abstract: The RNA recognition motif (RRM) is the far most abundant RNA binding domain. In addition to the typical β1α1β2β3α2β4 fold, various sub-structural elements have been described and reportedly contribute to the high functional versatility of RRMs. The heterogeneous nuclear ribonucleoprotein L (hnRNP L) is a highly abundant protein of 64 kDa comprising four RRM domains. Involved in many aspects of RNA metabolism, hnRNP L specifically binds to RNAs containing CA repeats or CA-rich clusters. However, a comprehensive structural description of hnRNP L including its sub-structural elements is missing. Here, we present the structural characterization of the RRM domains of hnRNP L and demonstrate their function in repressing exon 4 of SLC2A2. By comparison of the sub-structural elements between the two highly similar paralog families of hnRNP L and PTB, we defined signatures underlying interacting C-terminal coils (ICCs), the RRM34 domain interaction and RRMs with a C-terminal fifth β-strand, a variation we denoted vRRMs. Furthermore, computational analysis revealed new putative ICC-containing RRM families and allowed us to propose an evolutionary scenario explaining the origins of the ICC and fifth β-strand sub-structural extensions. Our studies provide insights of domain requirements in alternative splicing mediated by hnRNP L and molecular descriptions for the sub-structural elements. In addition, the analysis presented may help to classify other abundant RRM extensions and to predict structure-function relationships.

PubMed: 26051023
DOI: 10.1016/j.jmb.2015.05.020

Experimental method

SOLUTION NMR