title: Crystal structure of the human heterogeneous ribonucleoprotein A18 RNA-recognition motif.
abstract: 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.
authors.affiliation: Department of Biochemistry and Molecular Biology, Center for Biomolecular Therapeutics, University of Maryland School of Medicine, 108 North Greene Street, Baltimore, MD 21201, USA.
authors.forename: Katherine
authors.initials: K
authors.lastname: Coburn
authors.affiliation: Department of Biochemistry and Molecular Biology, Center for Biomolecular Therapeutics, University of Maryland School of Medicine, 108 North Greene Street, Baltimore, MD 21201, USA.
authors.forename: Zephan
authors.initials: Z
authors.lastname: Melville
authors.affiliation: Department of Biochemistry and Molecular Biology, Center for Biomolecular Therapeutics, University of Maryland School of Medicine, 108 North Greene Street, Baltimore, MD 21201, USA.
authors.forename: Ehson
authors.initials: E
authors.lastname: Aligholizadeh
authors.affiliation: Department of Biochemistry and Molecular Biology, Center for Biomolecular Therapeutics, University of Maryland School of Medicine, 108 North Greene Street, Baltimore, MD 21201, USA.
authors.forename: Braden M
authors.initials: BM
authors.lastname: Roth
authors.affiliation: Department of Biochemistry and Molecular Biology, Center for Biomolecular Therapeutics, University of Maryland School of Medicine, 108 North Greene Street, Baltimore, MD 21201, USA.
authors.forename: Kristen M
authors.initials: KM
authors.lastname: Varney
authors.affiliation: Department of Radiation Oncology, Marlene and Stewart Greenebaum Comprehensive Cancer Center, University of Maryland School of Medicine, 655 West Baltimore Street, Baltimore, MD 21201, USA.
authors.forename: France
authors.initials: F
authors.lastname: Carrier
authors.affiliation: Department of Biochemistry and Molecular Biology, Center for Biomolecular Therapeutics, University of Maryland School of Medicine, 108 North Greene Street, Baltimore, MD 21201, USA.
authors.forename: Edwin
authors.initials: E
authors.lastname: Pozharski
authors.affiliation: Department of Biochemistry and Molecular Biology, Center for Biomolecular Therapeutics, University of Maryland School of Medicine, 108 North Greene Street, Baltimore, MD 21201, USA.
authors.forename: David J
authors.initials: DJ
authors.lastname: Weber
mesh_terms: D020816:Amino Acid Motifs; D001665:Binding Sites; D003001:Cloning, Molecular; D018360:Crystallography, X-Ray; D010450:Endopeptidases / Q000737:chemistry; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D005822:Genetic Vectors / Q000737:chemistry / Q000378:metabolism; D000076245:Heterogeneous Nuclear Ribonucleoprotein A1 / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D008958:Models, Molecular; D011485:Protein Binding; D000072756:Protein Conformation, alpha-Helical; D000072757:Protein Conformation, beta-Strand; D054730:Protein Interaction Domains and Motifs; D012313:RNA / Q000737:chemistry* / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D040681:Structural Homology, Protein
chemical_list: C491390:CIRBP protein, human; D000076245:Heterogeneous Nuclear Ribonucleoprotein A1; D016601:RNA-Binding Proteins; D011994:Recombinant Proteins; D012313:RNA; D010450:Endopeptidases; C099488:TEV protease
keywords: RNA-binding protein; RNA-recognition motif; crystal structure; heterogeneous ribonucleoprotein A18; hnRNP A18; tumor growth