möglich sobald bei der ZB eingereicht worden ist.
Proc. Natl. Acad. Sci. U.S.A. 106, 18521-18526 (2009)
The PUR protein family is a distinct and highly conserved class that is characterized by its sequence-specific RNA-and DNA-binding. Its best-studied family member, Pur-alpha, acts as a transcriptional regulator, as host factor for viral replication, and as cofactor for mRNP localization in dendrites. Pur-alpha-deficient mice show severe neurologic defects and die after birth. Nucleic-acid binding by Pur-alpha is mediated by its central core region, for which no structural information is available. We determined the x-ray structure of residues 40 to 185 from Drosophila melanogaster Pur-alpha, which constitutes a major part of the core region. We found that this region contains two almost identical structural motifs, termed "PUR repeats,'' which interact with each other to form a PUR domain. DNA-and RNA-binding studies confirmed that PUR domains are indeed functional nucleic-acid binding domains. Database analysis show that PUR domains share a fold with the Whirly class of nucleic-acid binding proteins. Structural analysis combined with mutational studies suggest that a PUR domain binds nucleic acids through two independent surface regions involving concave beta-sheets. Structure- based sequence alignment revealed that the core region harbors a third PUR repeat at its C terminus. Subsequent characterization by small-angle x-ray scattering (SAXS) and size-exclusion chromatography indicated that PUR repeat III mediates dimerization of Pur-alpha. Surface envelopes calculated from SAXS data show that the Pur-alpha dimer consisting of repeats I to III is arranged in a Z-like shape. This unexpected domain organization of the entire core domain of Pur-alpha has direct implications for ssDNA/ssRNA and dsDNA binding.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter crystal structure; dna binding; rna binding; fragile x-associated tremor; ataxia syndrome; single-stranded-dna; guide-rna; protein gbp21; model; transcription; identification; replication; association; complexes; mechanism
ISSN (print) / ISBN 0027-8424
Quellenangaben Band: 106, Heft: 44, Seiten: 18521-18526
Verlag National Academy of Sciences
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Structural Biology (STB)