6dhs | pdb_00006dhs
Structure of hnRNP H qRRM1,2
Structural highlights
DiseaseHNRH1_HUMAN Precursor T-cell acute lymphoblastic leukemia. FunctionHNRH1_HUMAN This protein is a component of the heterogeneous nuclear ribonucleoprotein (hnRNP) complexes which provide the substrate for the processing events that pre-mRNAs undergo before becoming functional, translatable mRNAs in the cytoplasm. Mediates pre-mRNA alternative splicing regulation. Inhibits, together with CUGBP1, insulin receptor (IR) pre-mRNA exon 11 inclusion in myoblast. Binds to the IR RNA. Binds poly(RG).[1] [2] Publication Abstract from PubMedMembers of the heterogeneous nuclear ribonucleoprotein (hnRNP) F/H family are multi purpose RNA binding proteins that participate in most stages of RNA metabolism. Despite having similar RNA sequence preferences, hnRNP F/H proteins function in overlapping and in some cases distinct cellular processes. The domain organization of hnRNP F/H proteins is modular consisting of N-terminal tandem quasi-RNA Recognition Motifs (F/HqRRM1,2) and a third C-terminal qRRM3 embedded between glycine-rich repeats. The tandem qRRMs are connected through a 10-residue linker with several amino acids strictly conserved between hnRNP H and F. A significant difference occurs at position 105 of the linker where hnRNP H contains a proline and hnRNP F an alanine. To investigate the influence of P105 on the conformational properties of hnRNP H, we probed the structural dynamics of its HqRRM1,2 domain with x-ray crystallography, NMR spectroscopy, and small angle x-ray scattering. The collective results best describe that HqRRM1,2 exists in a conformational equilibrium between compact and extended structures. The compact structure displays an electropositive surface formed at the qRRM1-qRRM2 interface. Comparison of NMR relaxation parameters, including Carr-Purcell-Meiboom-Gill (CPMG) relaxation dispersion, between HqRRM1,2 and FqRRM1,2 indicate that FqRRM1,2 primarily adopts a more extended and flexible conformation. Introducing the P105A mutation into HqRRM1,2 alters its conformational dynamics to favor an extended structure. Thus, our work demonstrates that the linker compositions confer different structural properties between hnRNP F/H family members that might contribute to their functional diversity. Differential Conformational Dynamics Encoded by the Inter-qRRM linker of hnRNP H.,Penumutchu S, Chiu LY, Meagher JL, Hansen AL, Stuckey JA, Tolbert BS J Am Chem Soc. 2018 Aug 18. doi: 10.1021/jacs.8b05366. PMID:30122033[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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