Solution NMR Structure of the eukaryotic RNA recognition motif, RRM1, from the heterogeneous nuclear ribonucleoprotein H from Homo sapiens, Northeast Structural Genomics Consortium (NESG) Target HR8614A

Ramelot, Theresa; Yang, Yunhuang; Pederson, Kari; Shastry, R.; Kohan, Eitan; Janjua, H.; Xiao, R.; Acton, Thomas; Everett, J.K.; Prestegard, James H.; Montelione, Gaetano T.; Kennedy, Michael A.

doi:10.13018/bmr18698

Cited by 1 publication

(1 citation statement)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Since our initial NMR study indicates that HqRRM1,2 populates a compact conformation, we proceeded to determine its solution structure. The coordinates of HqRRM1 are already deposited in the Protein Database (PDB entry 2LXU); therefore, we solved the structure of HqRRM2 and calculated structural models of HqRRM1,2.…”

Section: Resultsmentioning

confidence: 99%

Differential Conformational Dynamics Encoded by the Linker between Quasi RNA Recognition Motifs of Heterogeneous Nuclear Ribonucleoprotein H

et al. 2018

View full text Add to dashboard Cite

Members of the heterogeneous nuclear ribonucleoprotein (hnRNP) F/H family are multipurpose 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 indicates 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.

show abstract

Section: Resultsmentioning

confidence: 99%