3K44

Crystal Structure of Drosophila melanogaster Pur-alpha

Summary for 3K44

• Entry DOI: 10.2210/pdb3k44/pdb
• Descriptor: Purine-rich binding protein-alpha, isoform B, CHLORIDE ION, 1,2-ETHANEDIOL, ... (4 entities in total)
• Functional Keywords: pur-alpha, pur repeat, pur domain, whirly fold, dna binding protein, rna binding protein, nucleic acid binding protein
• Biological source: Drosophila melanogaster (Fruit fly)
• Total number of polymer chains: 4
• Total formula weight: 67656.00

Authors

Graebsch, A.,Roche, S.,Niessing, D. (deposition date: 2009-10-05, release date: 2009-10-27, Last modification date: 2024-02-21)

Primary citation

Graebsch, A.,Roche, S.,Niessing, D.
X-ray structure of Pur-alpha reveals a Whirly-like fold and an unusual nucleic-acid binding surface
Proc.Natl.Acad.Sci.USA, 106:18521-18526, 2009

PubMed Abstract: 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.

PubMed: 19846792
DOI: 10.1073/pnas.0907990106

Experimental method

X-RAY DIFFRACTION (2.1 Å)