title: The acidic domain is a unique structural feature of the splicing factor SYNCRIP.
abstract: The splicing factor SYNCRIP (hnRNP Q) is involved in viral replication, neural morphogenesis, modulation of circadian oscillation, and the regulation of the cytidine deaminase APOBEC1. It consists of three globular RNA-recognition motifs (RRM) domains flanked by an N-terminal acid-rich acidic sequence segment domain (AcD12-97 ) and a C-terminal domain containing an arginine-glycine-rich sequence motif (RGG/RXG box), which are located near to the N- and C-terminals, respectively. The acid-rich sequence segment is unique to SYNCRIP and the closely related protein hnRNP R, and is involved in interactions with APOBEC1. Here, we show that while AcD12-97 does not form a globular domain, structure-based annotation identified a self-folding globular domain with an all α-helix architecture, AcD24-107 . The NMR structure of AcD24-107 is fundamentally different from previously reported AcD molecular models. In addition to negatively charged surface areas, it contains a large hydrophobic cavity and a positively charged surface area as potential epitopes for intermolecular interactions.
authors.affiliation: Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, California, 92037.
authors.forename: Christine
authors.initials: C
authors.lastname: Beuck
authors.affiliation: Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, California, 92037.
authors.forename: James R
authors.initials: JR
authors.lastname: Williamson
authors.affiliation: Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, California, 92037.|Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, California, 92037.|Joint Center for Structural Genomics, http://www.jcsg.org.
authors.forename: Kurt
authors.initials: K
authors.lastname: Wüthrich
authors.affiliation: Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, California, 92037.|Joint Center for Structural Genomics, http://www.jcsg.org.
authors.forename: Pedro
authors.initials: P
authors.lastname: Serrano
mesh_terms: D000595:Amino Acid Sequence; D003001:Cloning, Molecular; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D034441:Heterogeneous-Nuclear Ribonucleoproteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D057927:Hydrophobic and Hydrophilic Interactions; D007700:Kinetics; D008958:Models, Molecular; D000072756:Protein Conformation, alpha-Helical; D054730:Protein Interaction Domains and Motifs; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D055672:Static Electricity; D013816:Thermodynamics
chemical_list: D034441:Heterogeneous-Nuclear Ribonucleoproteins; D011994:Recombinant Proteins; C425312:SYNCRIP protein, human
keywords: APSY-NMR; J-UNIO protocol; NMR structure determination; unique splicing factor domain