The vesicular stomatitis virus has an atypical membrane fusion glycoprotein (G) exhibiting a pH-dependent equilibrium between two forms at the virus surface. Membrane fusion is triggered during the transition from the high- to low-pH form. The structure of G in its low-pH form shows the classic hairpin conformation observed in all other fusion proteins in their postfusion conformation, in spite of a novel fold combining features of fusion proteins from classes I and II. The structure provides a framework for understanding the reversibility of the G conformational change. Unexpectedly, G is homologous to gB of herpesviruses, which raises important questions on viral evolution.

Glycoprotein G of the vesicular stomatitis virus triggers membrane fusion via a low pH-induced structural rearrangement. Despite the equilibrium between the pre- and postfusion states, the structure of the prefusion form, determined to 3.0 angstrom resolution, shows that the fusogenic transition entails an extensive structural reorganization of G. Comparison with the structure of the postfusion form suggests a pathway for the conformational change. In the prefusion form, G has the shape of a tripod with the fusion loops exposed, which point toward the viral membrane, and with the antigenic sites located at the distal end of the molecule. A large number of G glycoproteins, perhaps organized as in the crystals, act cooperatively to induce membrane merging.

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-␣, acts as a transcriptional regulator, as host factor for viral replication, and as cofactor for mRNP localization in dendrites. Pur-␣-deficient mice show severe neurologic defects and die after birth. Nucleic-acid binding by Pur-␣ 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-␣, 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 ␤-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 sizeexclusion chromatography indicated that PUR repeat III mediates dimerization of Pur-␣. Surface envelopes calculated from SAXS data show that the Pur-␣ 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-␣ has direct implications for ssDNA/ ssRNA and dsDNA binding.crystal structure ͉ DNA binding ͉ RNA binding ͉ fragile X-associated tremor ͉ ataxia syndrome