title: The acidic domain of hnRNPQ (NSAP1) has structural similarity to Barstar and binds to Apobec1.
abstract: Apobec1 edits the ApoB mRNA by deaminating nucleotide C(6666), which results in a codon change from Glutamate to stop, and subsequent expression of a truncated protein. Apobec1 is regulated by ACF (Apobec1 complementation factor) and hnRNPQ, which contains an N-terminal "acidic domain" (AcD) of unknown function, three RNA recognition motifs, and an Arg/Gly-rich region. Here, we modeled the structure of AcD using the bacterial protein Barstar as a template. Furthermore, we demonstrated by in vitro pull-down assays that 6xHis-AcD alone is able to interact with GST-Apobec1. Finally, we performed in silico phosphorylation of AcD and molecular dynamics studies, which indicate conformational changes in the phosphorylated form. The results of the latter studies were confirmed by in vitro phosphorylation of 6xHis-AcD by protein kinase C, mass spectrometry, and spectroscopic analyses. Our data suggest hnRNPQ interactions via its AcD with Apobec1 and that this interaction is regulated by the AcD phosphorylation.
authors.affiliation: Centro de Biologia Molecular Estrutural, Laboratório Nacional de Luz Síncrotron, Rua Giuseppe Máximo Scolfaro 10,000, C.P. 6192, 13084-971 Campinas, SP, Brazil.
authors.forename: Alexandre J C
authors.initials: AJ
authors.lastname: Quaresma
authors.forename: Sergio
authors.initials: S
authors.lastname: Oyama
authors.forename: João A R G
authors.initials: JA
authors.lastname: Barbosa
authors.forename: Jörg
authors.initials: J
authors.lastname: Kobarg
mesh_terms: D000071479:APOBEC-1 Deaminase; D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry; D001665:Binding Sites; D002942:Circular Dichroism; D003198:Computer Simulation; D003564:Cytidine Deaminase / Q000378:metabolism*; D034441:Heterogeneous-Nuclear Ribonucleoproteins / Q000737:chemistry* / Q000378:metabolism; D006639:Histidine / Q000378:metabolism; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism; D017434:Protein Structure, Tertiary; D016601:RNA-Binding Proteins / Q000737:chemistry; D016415:Sequence Alignment; D012694:Serine / Q000378:metabolism; D013050:Spectrometry, Fluorescence; D040681:Structural Homology, Protein
chemical_list: C411647:A1CF protein, human; D001426:Bacterial Proteins; D034441:Heterogeneous-Nuclear Ribonucleoproteins; D016601:RNA-Binding Proteins; C425312:SYNCRIP protein, human; C033223:polyhistidine; C057438:barstar protein, Bacillus amyloliquefaciens; D012694:Serine; D006639:Histidine; D011493:Protein Kinase C; D000071479:APOBEC-1 Deaminase; C000605089:APOBEC1 protein, human; D003564:Cytidine Deaminase