Crystal structure of the human heterogeneous ribonucleoprotein A18 RNA-recognition motif

Acta Crystallogr F Struct Biol Commun. 2017 Apr 1;73(Pt 4):209-214. doi: 10.1107/S2053230X17003454. Epub 2017 Mar 22.


The heterogeneous ribonucleoprotein A18 (hnRNP A18) is upregulated in hypoxic regions of various solid tumors and promotes tumor growth via the coordination of mRNA transcripts associated with pro-survival genes. Thus, hnRNP A18 represents an important therapeutic target in tumor cells. Presented here is the first X-ray crystal structure to be reported for the RNA-recognition motif of hnRNP A18. By comparing this structure with those of homologous RNA-binding proteins (i.e. hnRNP A1), three residues on one face of an antiparallel β-sheet (Arg48, Phe50 and Phe52) and one residue in an unstructured loop (Arg41) were identified as likely to be involved in protein-nucleic acid interactions. This structure helps to serve as a foundation for biophysical studies of this RNA-binding protein and structure-based drug-design efforts for targeting hnRNP A18 in cancer, such as malignant melanoma, where hnRNP A18 levels are elevated and contribute to disease progression.

Keywords: RNA-binding protein; RNA-recognition motif; crystal structure; heterogeneous ribonucleoprotein A18; hnRNP A18; tumor growth.

MeSH terms

  • Amino Acid Motifs
  • Binding Sites
  • Cloning, Molecular
  • Crystallography, X-Ray
  • Endopeptidases / chemistry
  • Escherichia coli / genetics
  • Escherichia coli / metabolism
  • Gene Expression
  • Genetic Vectors / chemistry
  • Genetic Vectors / metabolism
  • Heterogeneous Nuclear Ribonucleoprotein A1 / chemistry*
  • Heterogeneous Nuclear Ribonucleoprotein A1 / genetics
  • Heterogeneous Nuclear Ribonucleoprotein A1 / metabolism
  • Humans
  • Hydrophobic and Hydrophilic Interactions
  • Models, Molecular
  • Protein Binding
  • Protein Conformation, alpha-Helical
  • Protein Conformation, beta-Strand
  • Protein Interaction Domains and Motifs
  • RNA / chemistry*
  • RNA / metabolism
  • RNA-Binding Proteins / chemistry*
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Structural Homology, Protein


  • CIRBP protein, human
  • Heterogeneous Nuclear Ribonucleoprotein A1
  • RNA-Binding Proteins
  • Recombinant Proteins
  • RNA
  • Endopeptidases
  • TEV protease